Osteoarthritis is a severe joint disease which mainly affects the knee and is characterized by joint pain and swelling. The condition is the result of heightened immune reaction at the joints leading to pain and stiffness and thus ultimately affecting the movement and comfort of the person.
Various treatments have been developed to ameliorate the symptoms and condition of osteoarthritis, however, they have been rendered ineffective in the long run. Turmeric, a golden colored spice, is one of the medicinal plants used for ages in various human ailments. Curcuminoids are bioactive components of turmeric and acts as a potential anti- inflammatory, immunomodulatory and antioxidant mediators. Curcumin C3 Complex® is a standardized turmeric extract that can ameliorate the conditions involving immune impairment. e present article discusses the implication of the curcuminoids in the osteoarthritic condition and gathers the evidence generated through systematically designed research studies in human subjects.
Summary : Osteoarthritis is a condition mainly influenced by immune components such as IL-2, IL-4, TNF-α, oxidative stress, antioxidant enzymes such as superoxide dismutase, catalase, and peroxidase. These help in the diagnosis and prognosis of the disease. In all the clinical studies it was evident that curcuminoid supplementation results in the decreased oxidative stress, alleviates the levels of proinflammatory cytokines, reduces tissue degradation, improves the regeneration, reduces the pain sensation and stiffness and reduces the dose requirement of the analgesic used to get temporary pain relief . Thus, it is strongly evident that Curcumin C3 Complex® can alleviate the conditions of osteoarthritis.
Curcuminoids: a golden solution for joint health - Muhammed Majeed, Shaheen Majeed, Mahadeva Nayak, Naveen Yelavare Puttaswamy - Nutracos June 2020

Abstract ; Coronavirus disease 2019 (COVID-19) outbreak is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with considerable mortality worldwide. The main clinical manifestation of COVID-19 is the presence of respiratory symptoms, but some patients develop severe cardiovascular and renal complications. There is an urgency to understand the mechanism by which this virus causes complications so as to develop treatment options. Curcumin, a natural polyphenolic compound, could be a potential treatment option for patients with coronavirus disease. In this study, we review some of the potential effects of curcumin such as inhibiting the entry of virus to the cell, inhibiting encapsulation of the virus and viral protease, as well as modulating various cellular signaling pathways. This review provides a basis for further research and development of clinical applications of curcumin for the treatment of newly emerged SARS-CoV-2.
Keyword: acute respiratory distress syndrome, curcuminoids, pulmonary fibrosis, viral infection
Potential effects of curcumin in the treatment of COVID-19 infection - Fatemeh Zahedipour, Seyede Atefe Hosseini, Thozhukat Sathyapalan, Muhammed Majeed, Tannaz Jamialahmadi, Khalid Al-Rasadi, Maciej Banach, Amirhossein Sahebkar - Phytotherapy Research. 2020;34:2911–2920. - DOI: 10.1002/ ptr.6738

A study that found benefits in metabolic syndrome patients given Sabinsa Corporation’s Curcumin C3 Complex was chosen by a panel of experts for the NutraIngredients University Research of the Year Award, announced last week in Geneva, Switzerland. This award, given to research that “takes the nutrition sector to a new level of understanding, with clear potential for the development of market changing products,” honored the study conducted at Mashhad University of Medical Sciences on C3 Complex and metabolic syndrome.
This study investigates the safety and efficacy of Curcumin C3 Complex in management of serum lipid concentrations in metabolic syndrome patients. The study results showed that Curcumin C3 Complex plus BioPerine® combination was well tolerated and also improved the serum lipid health in metabolic syndrome patients. (Panahi Y, Khalili N, Hosseini MS, Abbasinazari M, Sahebkar A. Lipid-modifying effects of adjunctive therapy with curcumioids-piperine combination in patients with metabolic syndrome: Results of a randomized controlled trial. ComplementaryTherapies in Medicine ; 2014; 22(5): 851-57).Eight-week supplementation with Curcumin C3 Complex and BioPerine was associated with a reduction of serum triglycerides, total cholesterol, serum low density lipoprotein-cholesterol, non-high density lipoprotein cholesterol, lipoprotein (a) and increase in the high density lipoprotein cholesterol (HDL) as compared to placebo.
"Curcumin C3 Complex is the most studied Curcumin ingredient on the market, primarily for inflammation, but this study is particularly significant in that it investigates another condition that has serious health implications in a large percentage of the population,” said Sabinsa founder Dr. Muhammed Majeed. “We thank NutraIngredients and their panel of experts for acknowledging the significance of this research and we thank the researchers for carrying out this important new study.”
Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial Yunes Panahi, Nahid Khalili, Mahboobeh Sadat Hosseini, Mohammad Abbasinazari, Amirhossein Sahebkar

Sabinsa's Curcumin C3 Complex® and BioPerine® Combination Used In Published Study On Metabolic Syndrome
Another significant study on the combination of Curcumin C3 Complex ® and BioPerine ®, Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: Results of a randomized controlled trial, by researchers at University of Medical Sciences, Mashhad, Iran, has been published in Complementary Therapies in Medicine
This study is the first trial investigating the efficacy and safety of adjunctive therapy with Curcuminoids-Piperine combination in patients with metabolic syndrome, receiving standard treatment. The results of the trial supported the effectiveness of the adjunctive therapy with significant decrease in serum concentration LDL-C, non-HDL-C, total cholesterol, triglyceride, Lp(a) and elevation in serum concentration of HDL-C in patients in comparison to the standard therapy alone. The present study also encouraged the efficacy of use of co-administering BioPerine® as a bioavailability enhancer. "This research indicates additional benefits of Curcumin beyond inflammation, giving increased value to C3 Complex as the body of science grows" said Shaheen Majeed, Sabinsa Marketing Director. "And once again the C3 Complex and BioPerine combination has been shown to be a safe and effective supplement blend that can help keep people healthy." Sabinsa's Curcumin C3 Complex® has been subject of over 72 research papers including 34 clinical studies published in peer reviewed journals. The combination of Curcumin C3 Complex® and BioPerine® has been studied in several independent clinical trials, including one published by Tufts University validating its safety and quality of ingredients and another on osteoarthritis from University of Medical Sciences, Mashhad, Iran

Sabinsa's Curcumin C3 Complex® and Bioperine® Combination Shows Significant Benefits In Osteoarthritis
In a significant study on the Curcumin C3 Complex® and BioPerine® combination, researchers at University of Medical Sciences, Mashhad, Iran observed considerable benefits of this combination in the management of knee osteoarthritis. The study was published in Phytotherapy Research and entitled Curcuminoid Treatment for Knee Osteoarthritis: A Randomized Double-Blind Placebo- Controlled Trial.
In this 8 week, 53 subjects, pilot randomized double blind placebo controlled parallel group study, patients suffering from mild to moderate knee osteoarthritis were administered Curcumin C3 Complex along with the natural bioavailability enhancer BioPerine (black pepper extract, piper nigrum) in three divided doses. BioPerine, trademarked and patented by Sabinsa, has been clinically studied for its safety and efficacy as a bioavailability enhancer for several dietary ingredients including Curcuminoids. The results show that the combination of Curcumin C3 Complex and BioPerine showed significant improvement in arthritic indices such as VAS (Visual Analogue Scale), WOMAC (Western Ontario and McMaster Universities Osteoarthritic Index) and LPFI (Lequesne's pain functional index) scores. Curcumin is a potent anti-inflammatory and scavenge free radicals, which cause oxidative stress thereby developing and progressing osteoarthritis. Study authors mention the combination of Curcumin with BioPerine as a novelty for this study, which improves the bioavailability by several mechanisms including the inhibition of curcuminoids glucuronidation in intestine and liver thus increasing the bioavailability of Curcuminoids . "We're excited to see one of the many potentials of curcumin re-enforced, especially for consumers and marketing companies that use our patented Curcumin C3 Complex and BioPerine ingredients for this activity," said Shaheen Majeed, Sabinsa Marketing Director. "Rather than using altered, oil based or other modified forms of curcumins that are out there in the marketplace, this study gives compelling evidence to simply add BioPerine for enhancing the uptake of curcumin."

Background: Oxidative stress and inflammation have been proposed as emerging components of metabolic syndrome (MetS). Curcuminoids are natural polyphenols with strong antioxidant and antiinflammatory properties.
Objective: To study the effectiveness of supplementation with a bioavailable curcuminoid preparation on measures of oxidative stress and inflammation in patients with MetS. Our secondary aim was to perform a meta-analysis of data from all randomized controlled trials in order to estimate the effect size of curcuminoids on plasma C-reactive protein (CRP) concentrations.
Methods: In this randomized double-blind placebo-controlled trial, 117 subjects with MetS (according to the NCEP-ATPIII diagnostic criteria) were randomly assigned to curcuminoids (n=59; drop-outs=9) or placebo (n=58; drop-outs=8) for eight weeks. Curcuminoids were administered at a daily dose of 1 g, and were co-supplemented with piperine (10 mg/day) in order to boost oral bioavailability. Serum activities of superoxide dismutase (SOD) and concentrations of malondialdehyde (MDA) and CRP were measured at baseline and at study end. Regarding the importance of CRP as a risk marker and risk factor of cardiovascular disease, a random-effects meta-analysis of clinical trials was performed to estimate the overall impact of curcuminoid therapy on circulating concentrations of CRP. The robustness of estimated effect size was evaluated using leave-one-out sensitivity analysis.
Results: Supplementation with curcuminoid-piperine combination significantly improved serum SOD activities (p max 0.001) and reduced MDA (p max 0.001) and CRP (p max 0.001) concentrations compared with placebo. Quantitative data synthesis revealed a significant effect of curcuminoids vs. placebo in reducing circulating CRP concentrations (weighed mean difference: -2.20 mg/L; 95% confidence interval [CI]: -3.96, -0.44; p = 0.01). This effect was robust in sensitivity analysis.
Conclusions: Short-term supplementation with curcuminoid-piperine combination significantly improves oxidative and inflammatory status in patients with MetS. Curcuminoids could be regarded as natural, safe and effective CRP-lowering agents.
Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis Yunes Panahi, Mahboobeh Sadat Hosseini, Nahid Khalili, Effat Naimi, Muhammed Majeed, Amirhossein Sahebkar

Background: Dyslipidemia is an established feature of metabolic syndrome (MS) that is associated with an increased risk of atherosclerotic cardiovascular disease. Curcuminoids are natural products with anti - atherosclerotic and lipid - modifying effects but their efficacy in patients with MS has not yet been tested.
Objective : To investigate the effects of bioavailability - enhanced curcuminoids, as adjunctive to standard of care, on serum lipid concentrations in patients with MS.
Method : Patients diagnosed with MS according to the NCEP-ATPIII criteria who were receiving standard of care were assigned to either curcuminoids (C3 complex®; 1000mg/day; n = 50) or placebo (n = 50; matched with drug capsules in shape and color) for 8 weeks. In order to improve the oral bioavailability, curcuminoids were co-administered with piperine (bioperine®) in a ratio of 100:1. Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, small dense LDL (sdLDL), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of 8-week treatment period.
Results: Curcuminoids were more effective than placebo in reducing serum LDL-C, non-HDL-C, total cholesterol, triglycerides and Lp(a), and elevating HDL-C concentrations. However, changes in serum sdLDL levels were found to be comparable between the study groups. The effects of curcuminoids on triglycerides, non-HDL-C, total cholesterol and Lp(a) remained significant after adjustment for baseline values of lipids and body mass index.
Conclusion: Curcuminoids-piperine combination is an efficacious adjunctive therapy in patients with MS and can modify serum lipid concentrations beyond what is achieved with standard of care.
Lipid-modifying effects of adjunctive therapy with curcuminoids - piperine combination in patients with metabolic syndrome: Results of a randomized controlled trial - Complementary Therapies in Medicine (2014), Yunes Panahi, Nahid Khalili, Mahboobeh Sadat Hosseini, Mohammad Abbasinazari, Amirhossein Sahebkar

The liver is a central controller and co-ordinator of the body’s metabolism. It has a strong influence on all the organs and itself is influenced by other organs viz., gut, pancreas, and adipose tissue. The gut is an important organ that influences the liver both directly and indirectly. The role of the gut-liver axis in the pathophysiology of certain liver conditions, such as non-alcoholic fatty liver disease, is well understood. Studies show that gut dysbiosis exaggerates the fatty liver condition by increased inflammation. The treatment strategies for non-alcoholic fatty liver disease include amelioration of metabolic imbalance, insulin resistance, dyslipidaemia, and gut dysbiosis. Because of the multi-pathological influences involved in the development of the fatty liver condition, there is no single drug that can completely cure the condition.
A deep body of research concluded that the medicinal benefits of turmeric are attributed to the curcuminoids. Various compounds viz. curcumin, dimethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are the important components comprising turmeric’s curcuminoids. These curcuminoids influence various aspects of the physiological system which ultimately results in enhanced health in humans. Curcuminoids are beneficial in improving or ameliorating metabolic imbalances viz., management of healthy blood sugar levels, weight management, and other metabolic disorders.
Curcuminoids have been shown to ameliorate the altered levels of serum adipokines in type-2 diabetic subjects. The study was conducted in 118 subjects for 12 weeks. The serum levels of adipokines viz., adiponectin, leptin, ghrelin, and tumor necrosis factor-alpha (TNF-alpha) were measured at baseline and the end of the study period. Results showed that curcuminoids.
The results of the study showed that curcuminoid supplementation reduced the total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and improved the levels of HDL. The study concluded that curcuminoid supplementatin could contribute to a reduced risk of cardiovascular events in dyslipidemia patients since it reduced the serum levels of atherogenic lipid indices.
Curcuminoids can act at various targets for the management of non-alcoholic fatty liver disease viz normalize the serum lipoproteins, reduce the insulin resistance, improve serum glycemic balance, reduce oxidative stress, and improve the gut microbiome health, and improve the liver health through attenuation of liver oxidative stress. Hence, curcuminoids are potential agents which could ameliorate non-alcoholic fatty liver disease.
Curcuminoids : a golden solution for non-alcoholic fatty liver, Muhammed Majeed, Shaheen Majeed, Mahadeva Nayak, Naveen Yelavare Puttaswamy, Nutracos September/october 2020

Diabetes, a major health risk by itself and by engendering several other co-­‐morbid conditions, is estimated to afflict about 8.3% of the American population. It is expected to climb further with prevailing food habits and lifestyle, further inflating the estimated burden of $245 billion on the economy. While diverse types of medications are available, there is still a need for nutritional intervention to control this pernicious disease. Oxidative burden is well-­‐recognized component of diabetes.
In this 2016 paper published on the results of a clinical trial on 118 type II diabetes subjects, the combination of C3 Complex and BioPerine (daily dose of 1 g and 10 mg, respectively) for three months significantly reduced serum malondialdehyde (MDA) with increase in serum total antioxidant capacity (TAC) and the activity of superoxide dismutase (SOD) in patients with type-­‐2 diabetes (T2DM). The study was designed as a randomized, double-­‐blind, placebo-­‐controlled trial with a parallel-­‐group design.
“Diminution of the well-­‐marker of oxidative stress, MDA, as well as the increase in TAC and SOD, body’s natural and most powerful anti-­‐oxidant enzymes, are prized goals indicative of the body’s response to undo the damage wreaked by hyperglycemia,” said Nagabhushanam Kalyanam, PhD, President (R / D), Sabinsa. “The growing body of science indicates this combination can play a significant role in supporting the health of diabetes patients, and we intend to pursue this line of study further.”
As early as in 2008, Sabinsa’s C3 Complex was used in animal studies by researchers from Columbia University [Endocrinology 149(7), 3549-­‐3558 (2008)} who concluded this curcuminoid admixture ameliorated diabetes in obese, leptin-­‐hormone deficient mice as determined by glucose tolerance test and glycated hemoglobin (HbA1c) levels. Similarly, University of Auburn’s researchers [Biochem Biophys Res Comm. 388, 377-­‐382 (2009)] found that Curcumin C3 Complex not only inhibited gluconeogenic gene expression in cells but also inhibited alpha-­‐glucosidase activity among others to improve diabetic conditions.

This study examined the effects of placebo, Turmeric powder in combination with BioPerine®, and Curcumin C3 Complex® in combination with BioPerine as actives. Sabinsa supplied Curcumin C3 Complex and BioPerine material to the research team, which was affiliated with several universities in the USA.
The study found that while both turmeric and curcuminoids have similar qualitative effects on the intestinal bacterial population, curcuminoids had a far larger quantitative effect, indicating that curcuminoids in turmeric are the decisive components in influencing the bacterial population. Thus, curcuminoids have an unique role and effect on the gut microbiome in the sense that they are not only metabolized to useful products such as reductive metabolites like tetrahydrocurcumin (by E. coli) and to demethylated curcuminoids (by Blautia sp.) as demonstrated by previous researchers, but they also increase the population of several species of gut microbiome.
Unlike prebiotics, which are necessarily driven by catabolism of sugar components, the researchers attribute the “prebiotic-like” effects of curcuminoids to suitable alterations of host physiology congenial to the growth of beneficial microbiota. Among the subjects in the study were responders and non-responders. The researchers theorized that subjects with poor absorption of the actives are probably the best responders.
Curcuminoids provided by Curcumin C3 Complex had a positive influence on Bacteroidetes among others thus demonstrating for the first time in a human clinical study the beneficial effect of curcuminoids on gut microbiota population redistribution. The study used as much 6g/day of Curcumin C3 Complex, further reinforcing the existing safety data on the product.
“To my knowledge this is the first human study on curcuminoids on human microbiome,” said Dr. Majeed. “It constitutes a new direction in curcumin research, adding to the extensive body of science that has already been published on quite a few different benefits. It’s important to point out that Curcumin C3 Complex and BioPerine are both unique ingredients, so it should not be assumed that the same effects would be observed universally with all generic material.”
Turmeric tablets, curcumin tablets, and placebo tablets were provided by Sabinsa Corporation (East Windsor, NJ). The turmeric tablets contained 1000 mg turmeric root (Curcuma longa) plus 1.25 mg black pepper–derived extract of piperine alkaloid (BioPerine). The curcumin tablets contained 1000 mg of curcumin (Curcumin C3 Complex) plus 1.25 mg black pepper BioPerine.
Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study - Christine T. Peterson PhD et al published in the Journal of Evidence-Based Integrative Medicine (Volume 23: 1-8)

Malignant Mesothelioma (MM) is an aggressive form cancer primarily associated with exposure to asbestos fibers. Long latency, non-specific clinical symptoms, and resistance to chemotherapy render MM especially dangerous.
The study, Curcumin C3 Complex / BioPerine has antineoplastic activity in mesotherlioma: an in vitro and in vivo analysis by Francesco Di Meo et al (J Exp Clin Cancer Research 2019; 38:Article no. 360 ), explored the combined use of CBP in drug susceptible and drug-resistant MM cancer cell-types. The researchers found that CBP worked well in synergistically impairing the cancer cell viability, cellular self-renewal ability, cell proliferation rate, and cell migration as assessed by wound-healing assay. Onset of apoptosis of cancer cells in drug susceptible and resistant ones was also determined occur by activation of intrinsic pathway through altered ratio of Bax/BCl2 proteins. Efficacy of CBP was further demonstrated in a xenograft model of MM. Low cancer cell proliferation (as judged by Ki-67 levels), higher TUNEL score indicating enhanced apoptosis and reduced angiogenesis in tumor cells were noted in the animal graft study.
The authors noted that it might be possible to include CBP administration with drug regimens for MM similar to an earlier colorectal cancer study of FOLFOX with C3 Complex (Journal of Nutrition: doi/ 10.1093/ jn/ nxz029/5499032).
“Research suggesting that utilization of our flagship ingredients in combination with standard pharmacological therapies may pave the way to developing alternative and more effective treatment regimens for MM is encouraging, as its prognosis, at present, remains poor,” said Sabinsa’s founder, Dr. Muhammed Majeed. “We continue to be gratified that researchers throughout the world are investigating our Curcumin C3 Complex and BioPerine for advances such as this.”
Background: A major limitation in the treatment for malignant mesothelioma is related to serious side effects caused by chemotherapeutics and to the development of cancer-resistance. Advances in cancer therapies have been reached thanks to the introduction of alternative approaches, such as the use of phytochemicals. Curcumin C3 complex® / Bioperine® is a commercially standardized extract containing a ratio-defined mixture of three curcuminoids and piperine that greatly increase its bioavailability. Interestingly, the anticancer effect of this formulation has been described in different studies and several clinical trials have been started, but to our knowledge none refers to human mesothelioma.
Methods: Curcumin C3 complex® / Bioperine® anticancer effect was evaluated in vitro in different human mesothelioma cell lines analysing cell proliferation, colony-forming assay, wound healing assays, invasion assay and FACS analysis. In vivo anticancer properties were analysed in a mesothelioma xenograft mouse model in CD1 Nude mice.
Results: Curcumin C3 complex® / Bioperine® in vitro induced growth inhibition in all mesothelioma cell lines analysed in a dose- and time-depended manner and reduced self-renewal cell migration and cell invasive ability. Cell death was due to apoptosis. The analysis of the molecular signalling pathway suggested that intrinsic apoptotic pathway is activated by this treatment. This treatment in vivo delayed the growth of the ectopic tumours in a mesothelioma xenograft mouse model.
Conclusions: Curcumin C3complex® / Bioperine® treatment strongly reduces in vitro tumorigenic properties of mesothelioma cells by impairing cellular self-renewal ability, proliferative cell rate and cell migration and delays tumor growth in xenograft mouse model by reducing angiogenesis and increasing apoptosis. Considering that curcumin in vivo synergizes drug effects, its administration to treatment regimen may help to enhance drug therapeutic efficacy in mesothelioma. Our results suggest that implementation of standard pharmacological therapies with novel compounds may pave the way to develop alternative approaches to mesothelioma.
Keywords: Mesothelioma, Curcumin C3 complex, Intrinsic apoptosis, Tumor growth inhibition
Curcumin C3 complex® / Bioperine® has antineoplastic activity in mesothelioma: an in vitro and in vivo analysis - Francesco Di Meo, Stefania Filosa, Michele Madonna, Gerarda Giello, Alba Di Pardo, Vittorio Maglione, Alfonso Baldi, and Stefania Crispi - Journal of Experimental & Clinical Cancer Research (2019) 38:360

Abstract Background Oxidative stress has a key role in the pathogenesis of type II diabetes mellitus (T2DM) and its vascular complications. Antioxidant therapy has been suggested as a potential approach to blunt T2DM development and progression. The aim of this study was to assess the effects of supplementation with curcuminoids, which are natural polyphenolics from turmeric, on oxidative indices in diabetic individuals.
Methods In this randomized double-blind placebo-controlled trial, 118 subjects with T2DM were randomized to curcuminoids (1000 mg/day co-administered with piperine 10 mg/day) or matching placebo for a period of 8 weeks. Serum total antioxidant capacity, superoxide dismutase (SOD) activities and malondialdehyde (MDA) concentrations were measured at baseline and after the supplementation period.
Results : Curcuminoids supplementation caused a significant elevation in serum total antioxidant capacity (TAC) (p\0.001) and SOD activities (p\0.001), while serum MDA levels were significantly reduced compared with the placebo group (p\0.001). These results remained statistically significant after adjustment for potential confounders (baseline differences in body mass index and fasting serum insulin).
Conclusion : The present results support an antioxidant effect of curcuminoids supplementation in patients with T2DM, and call for future studies to assess the impact of these antioxidant effects on the occurrence of diabetic complications and cardiovascular endpoints
Keywords Curcumin, Diabetes mellitus, Oxidative stress, Malondialdehyde, Total antioxidant capacity, Superoxide dismutase
Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial - Inflammopharmacol - DOI 10.1007 / s10787 - 016 - 0301 - 4 Inflammopharmacology, Yunes Panahi, Nahid Khalili, Ebrahim Sahebi, Soha Namazi, Maryam Saberi Karimian, Muhammed Majeed, Amirhossein Sahebkar

The trial involved a total of 140 patients with mild, moderate, and severe symptoms of COVID-19 in a hospital exclusively for COVID-19 patients. While mild/moderately symptomatic patients were admitted to the wards, patients with severe symptoms were in the hospital's intensive-care unit. The treatment outcome was gauged by the pre-defined primary and secondary outcome measures. Patients in the group who received the C3 Complex + BioPerine adjuvant treatment showed quicker symptomatic recovery (of fever, cough, sore throat, breathlessness), had a lower incidence of red-flag signs, and better ability to maintain oxygen saturation min 94% on room air only. The D-dimer levels were less severe in C3-group than in the non-C3-group. While some patients in the moderate non-C3 group needed Tocilizumab injections, none in the corresponding moderate C3-group required such intervention. Fewer in the C3-group needed mechanical ventilator support or suffered thromboembolic episodes than in the non-C3 group.
Background: Coronavirus disease-2019 (COVID-19) has a wide range of pathophysiological effects. Curcumin, an active constituent of Curcuma longa (turmeric), has several properties, including anti-inflammatory, antioxidant, antiviral, antithrombotic, and anti-proliferative effects, which make it a promising candidate for the symptomatic treatment of COVID-19.
Objective: We aimed to determine the effects of curcumin administered with piperine (to optimize absorption) on symptoms in patients with COVID-19 in a double-blind, randomized, controlled trial at a 30-bed dedicated COVID Health Center (DCHC) in Maharashtra, India.
Methods: In addition to conventional COVID-19 treatment, patients in the control group received a dose of probiotics twice a day, and patients in the study group received curcumin (525 mg) with piperine (2.5mg) in tablet form twice a day. The effects of curcumin/piperine treatment on primary and secondary outcomeswere assessed for the duration of hospitalization.
Results: Patients with mild, moderate, and severe symptoms who received curcumin/ piperine treatment showed early symptomatic recovery (fever, cough, sore throat, and breathlessness), less deterioration, fewer red flag signs, better ability to maintain oxygen saturation above 94% on room air, and better clinical outcomes compared to patients of the control group. Furthermore, curcumin/piperine treatment appeared to reduce the duration of hospitalization in patients with moderate to severe symptoms, and fewer deaths were observed in the curcumin/piperine treatment group.
Conclusions: Administration of oral curcumin with piperine as an adjuvant symptomatic therapy in COVID-19 treatment could substantially reduce morbidity and mortality, and ease the logistical and supply-related burdens on the healthcare system. Curcumin could be a safe and natural therapeutic option to prevent Post-Covid thromboembolic events.
Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial, Kirti S Pawar, Rahul N Mastud, Satheesh K Pawar, Samragni S Pawar, Rahul R Bhoite, Ramesh R Bhoite, Meenal V Kulkarni and Aditi R Deshpande, Frontiers in Pharmacology, May 2021, Volume 12

In this clinical trial, researchers studied the effects of the administration of Curcumin C3 Complex and BioPerine in combination on the levels of the cytokines leptin and adiponectin in critically ill patients with traumatic brain injury (TBI). In a total of sixty-two patients, supplementation with 500 mg C3 Complex and 5 mg BioPerine daily showed a statistically significant decrease in the pro-inflammatory cytokine leptin in the treatment group compared with the placebo group.
While leptin is often associated with food intake and energy expenditure, its importance in aging conditions, serious illness, and stressful injuries is increasingly recognized.
Simultaneously the researchers also monitored the levels of the beneficial anti-inflammatory cytokine adiponectin. They commented that the increase in adiponectin did not reach statistical significance, presumably due to the short 7-day duration of this trial. They also pointed to other trial results in which longer durations of curcuminoids administration resulted in adiponectin level increases.
Abstract: Previous studies have shown a beneficial effect of curcuminoids supplementation on serum concentrations of adipokines; however, there are no published studies that have examined this effect among critically ill patients. We aimed to assess the effects of supplementation with curcuminoids on serum concentrations of leptin and adiponectin in critically ill patients with traumatic brain injury (TBI). In this trial, 62 critically ill patients with TBI, aged 18–65 years, were randomly allocated to receive either 500 mg/day curcuminoids (co‐administered with 5 mg/day piperine) or matched placebo for 7 days. Patients in both intervention groups received routine treatments for TBI as well as enteral nutrition. Serum concentrations of leptin and adiponectin were measured at baseline and at the end of trial. We found a significant reduction in serum levels of leptin in both curcuminoids (47.1%) and placebo (22.8%) groups; though the magnitude of reduction was greater in the former (p  max  .05). Supplementation with curcumioinds was not found to alter serum concentrations of adiponectin (p  min  .05). Supplementation with curcumioinds significantly reduced serum levels of leptin but had no significant effect on adiponectin levels in critically ill patients with TBI. Further clinical trials, particularly those with a long‐term period, are needed to confirm our findings.
Effects of supplementation with curcuminoids on serum adipokines in critically ill patients: a randomized double‐blind placebo‐controlled trial Mahdi Shadnoush Hoda Zahedi Abdolreza Norouzy Amirhossein Sahebkar Omid Sadeghi Atabak Najafi Saeed Hosseini Mostafa Qorbani Arezoo Ahmadi Seyed Hossein Ardehali, Phytotherapy Research, 06/2020

Background : Functional dyspepsia is the main cause of upper abdominal discomfort affecting 5–10% of the world population. Despite various therapeutic approaches, up to 50% of patients with functional dyspepsia seek alternative treatments. In the present study we evaluated the effect of curcumin supplementation along with famotidine therapy on severity of functional dyspepsia. A total of 75 patients with functional dyspepsia according to Rome III criteria were allocated into intervention (N = 39) or control (N = 36) groups. The intervention group was treated with a combination of 500 mg curcumin and 40 mg famotidine daily for 1 month. The control group received placebo and 40 mg famotidine. Severity of dyspepsia symptoms was determined using the Hong Kong questionnaire at baseline, after the 1 month treatment and after a 1 month follow-up. The presence of H. pylori antigens in the stool samples was also investigated in all subjects. No significant difference was observed between intervention and control groups in biochemical indices, severity of dyspepsia and rate of H. pylori infection. A significant decrease was observed in severity of dyspepsia (p max 0.001) and rate of H. pylori infection (p = 0.004) immediately after the treatment and follow-up in the curcumin intervention group. This study indicated that curcumin therapy could be a favorable supplementation in the symptom management of functional dyspepsia. Moreover, curcumin could help efficient eradication of H. pylori in these patients.
Conclusion : The findings of this study revealed that adding curcumin as an adjunct therapy not only improves clinical symptoms of dyspepsia but also eradicates the rate of H. pylori infection. Considering the good safety profile of curcumin and its pleiotropic actions, it could be used as an efficacious agent in functional dyspepsia. However, additional larger and long-term investigations are needed to confirm these promising results and the potential role of adjunctive curcumin therapy in the management of functional dyspepsia. Finally, it seems that the presence of H. pylori infection is a confounding factor in functional dyspepsia and the efficacy of curcumin on H. pylori eradication was not fully established. The impact of the presence H. pylori infection on the efficacy of curcumin in ameliorating the symptoms of functional dyspepsia needs to be further scrutinized.
Keywords : Functional dyspepsia · Curcumin · H. pylori
Effect of Curcumin on Severity of Functional Dyspepsia: a Triple Blinded Clinical Trial, Yunes Panahi, Ashraf Karbasi, Ghasem Valizadegan, Nayyereh Ostadzadeh, Sara Saffar Soflaei, Tannaz Jamialahmadi, Muhammed Majeed, and Amirhossein Sahebkar, Advances in Experimental Medicine and Biology 1308, March 2021

Background: Growing evidence suggests epigenetic dysregulation may play a role in schizophrenia. We hypothesize that curcumin (Diferuloylmethane) extracted from Curcuma Longata, shown to function as a pan-histone deacetylease(HDAC) inhibitor, may offer potential therapeutic benefits in schizophrenia treatment.
Objective: We chose standardized Curcumin C-3 complex combined with Bioperine™: SupercuminTM to examine the efficacy of Curcumin in improving the core positive and negative symptoms and cognitive deficits in patients diagnosed as schizophrenia.
Method: We recruited community dwelling schizophrenia patients with persistent negative symptoms (Scale for Assessment of Negative Symptoms: SANS score min 30) to participate in the open-label-parallel-group-randomized study.
Results: We randomized 17 subjects (mean age: 39·9 years, male/female: 13/4) into Group 1(SupercurcuminTM daily 1 gm ) and Group 2(SupercurcuminTM 4 gm daily) for 16 weeks, and 15/17 subjects completed the study. The subjects were maintained on current antipsychotic therapy. We found that Group 1 Group 2 significantly improved the total and general psychopathology sub-scales pf PANSS (Positive and Negative Symptoms scale). Within group pre- and post-treatment comparison showed standardized-mean-differences in total PANSS score and PANSS-general psychopathology were significant for Group 1 (p max 0.003 and p max 0.002) and for Group 2 (P max 0.01 and p max 0.016). We found Cohen’s d-effect size favored Supercurcumin™ in PANSS-positive, PANSS-negative subscale. Both groups exhibited improvement in selected cognitive domains. SupercurcuminTM was well tolerated with no serious adverse events.
Conclusion: Our study demonstrates for the first time augmenting effects of curcumin combined with piperine in schizophrenia. Randomized controlled trials are warranted to corroborate efficacy of curcumin schizophrenia.
DISCUSSION : Super curcuminTM, corroborates the claim that pepper increases the bioavailability of curcumin by as much as 2,000 x fold. The sub-optimal pharmacokinetic profile of curcumin most likely explains the discrepant findings of studies of oral curcumin formulations in Alzheimer dementia. Curcumin belongs the master regulator of multiple epigenetics targets implicated in neuro-epigenomes-driven chromatin remodeling and neuro-inflammation pathways genes, and plasticity gene. A recent PET imaging study with the specific HDAC ligand: [C14]-Martin stat [50] has found that schizophrenia subjects exhibited altered HDAC expression in the dorsal-lateral prefrontal cortex (DLPFC) compared with healthy control. HDAC expression positively correlated with cognitive performance scores in schizophrenia and schizoaffective disorder. For optimizing curcumin, nanotechnology can optimize targeted drug delivery system. Repurposing Liposome-based-curcumin formulation (LipocurcTm, Sign Path Pharm. PA USA) from oncology to CNS disorders can be transformative approach in treatment refractory schizophrenia. Phase I trial of LipocurcTM in normal healthy control subjects has demonstrated a very favorable safety profile. Taken together, our preliminary study highlights pharmacological targeting of dysregulation of epigenetics signaling of HDAC inhibition may be a heuristic roadmap in developing novel therapeutics in schizophrenia.
KEYWORDS: Curcumin; Epigenetics; Schizophrenia; positive, negative symptoms; cognition; bioperine: pepper; Histone deacetylase
Exploratory Study of Curcumin isolated from Turmeric Curcuma Longa, the Putative Histone Deacetylase Inhibitor, as added-on strategy to antipsychotics in treating negative symptoms and Neuro-cognitive deficits in Schizophrenia, Simon Chiu, Michel Woodbury-Farina; Kristen Terpstra3; Vladimir Badmaev, … 09/2019, International Journal Foundation

In a detailed study that involved both in vitro and in vivo models, these researchers compared both anti - inflammatory and anti - oxidant activity, the two premier activities for which Curcuminoids are noted, among five brands on the market. They concluded that Sabinsa’s C3 Complex® was “consistently the most active sample.”
The anti-inflammatory comparison involved the study of depression in the expression of the proinflammatory cytokines such as TNF-α, IL-6, IL-10 etc with C3 Complex out in the front. Also C3 Complex® led in reducing acute‐inflammation in a xylene-induced acute inflammation of the mouse ear model. Again C3 Complex led the pack in hepatoprotection reflective of the anti-­‐oxidant activity examined in a CCl4 induced hepatic damage in animals leading them to deduce “We can conclude that despite the fact that curcumin truly represents a biologically active natural molecule, its activity differs widely based on the type of sample. Clearly, not all curcumins available were created equal.”
“Curcumin is more than just one of Sabinsa’s ingredients; it holds a special place in our hearts and minds because it can significantly enhance human health,” said Shaheen Majeed, Marketing Director, Sabinsa. “Many people here have worked extremely hard to produce the best form of curcumin to deliver health benefits, and are gratified to have their efforts confirmed by independent research. This is more evidence that the specific form of curcumin chosen for a formula is an important decision.

Abstract : Curcumin is a turmeric-based compound with potential health benefits. In our study, we focused on the anti-inflammatory effects of curcumin. We investigated the effect of oral supplementation with curcumin on production of cytokines such as IL-4, IL-10, IFN-γ, and TNF-α both in vitro and in vivo. Mice supplemented with curcumin showed significant protection against LPS-induced endotoxemia effects and against CCL4-induced hepatotoxicity. In addition, we directly compared the biological effects of five different types of curcumin, showing that only some of them have significant biological activity.
Keywords: Curcumin; Inflammation; Cytokines; Liver; Hepatotoxicity
Comparison of five curcumin brands : Not all curcuminoid products on the market are the same, according to independent academic researchers at the University of Louisville, Louisville, Kentucky. Their study, Strong Anti ‐ Inflammatory Effects of Curcumin, was published in the Journal of Nutrition and Health Sciences (JNutrHealthSci16 - 205 Vetvicka V, University of Louisville, Department of Pathology, Louisville, KY).

Discussion : Colorectal cancer (CRC) is one of the major causes of human mortality and morbidity. Colitis- accelerated colon cancer (CAC) is a sub-type of CRC that is also closely associated with inflammatory bowel disease (IBD). Although aspirin has been widely investigated as a chemopreventive agent for CAC and different types of CRC, the potential side-effect of gastrointestinal bleeding has been a concern in long-term high-dose aspirin therapy. In this new study on animals, researchers at Rutgers discovered that co-administration of Curcumin C3 Complex® and aspirin helps to lower the dose of aspirin by 50% rendering this therapy feasible without adverse effects. It has been known earlier that Curcumin C3 complex® is non-toxic at all tested doses.
Additionally aspirin and C3 Complex combination modulated a larger gene sets than the single agent treatment. These genes were involved in several canonical pathways important in the inflammatory network and liver metastasis in CAC. Also this was the first study is first of its kind in an Azoxymethane(AOM)/DSS (Dextran sulfate sodium)-induced CAC. "Extensive research on Curcumin C3 Complex continues to reveal additional applications and benefits, which fosters further studies added to the large body of science on C3 Complex," said Sabinsa founder Dr. Muhammed Majeed. "The range of health benefits scientific investigation has identified continues to inspire researchers across the globe."
Abstract : Colorectal cancer (CRC) remains the leading cause of cancer-related death in the world. Aspirin (ASA) and curcumin (CUR) are widely investigated chemopreventive candidates for CRC. However, the precise mechanisms of their action and their combinatorial effects have not been evaluated. The purpose of the present study was to determine the effect of ASA, CUR, and their combination in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-accelerated colorectal cancer (CAC). We also aimed to characterize the differential gene expression profiles in AOM/DSS-induced tumors as well as in tumors modulated by ASA and CUR using RNA-seq. Diets supplemented with 0.02% ASA, 2% CUR or 0.01% ASA + 1% CUR were given to mice from 1 week prior to the AOM injection until the experiment was terminated 22 weeks after AOM initiation. Our results showed that CUR had a superior inhibitory effect in colon tumorigenesis compared to that of ASA. The combination of ASA and CUR at a lower dose exhibited similar efficacy to that of a higher dose of CUR at 2%. RNA isolated from colonic tissue from the control group and from tumor samples from the experimental groups was subjected to RNA-seq. Transcriptomic analysis suggested that the low-dose combination of ASA and CUR modulated larger gene sets than the single treatment. These differentially expressed genes were situated in several canonical pathways important in the inflammatory network and liver metastasis in CAC. We identified a small subset of genes as potential molecular targets involved in the preventive action of the combination of ASA and CUR. Taken together, the current results provide the first evidence in support of the chemopreventive effect of a low-dose combination of ASA and CUR in CAC. Moreover, the transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from normal colonic tissue to tumor development as well as the cancer inhibitory effects and potential molecular targets of ASA and CUR.
Keywords : Colitis-associated colorectal cancerAspirinCurcuminRNA-seq
Mechanisms of colitis-accelerated colon carcinogenesis and its prevention with the combination of aspirin and curcumin: Transcriptomic analysis using RNA-seq, Yue Guo, Zheng-Yuan Su, Chengyue Zhang, John M.Gaspar, Rui Wang, Ronald P. Hart, Michael P.Verzi, Ah-Ng Tony Kong, Biochemical Pharmacology, Volume 135, 1 July 2017, Pages 22-34

The study undertook to provide a comprehensive bibliometric overview of published research on curcumin, complementing the previous reviews and meta-analyses on its potential health benefits. The initial search returned 18,036 manuscripts with more than half published since 2014. The major contributing countries were the United States, China, India, Japan, and South Korea, with the journals representing the scientific disciplines of biochemistry, chemistry, oncology, and pharmacology. Much of the literature focused on curcumin’s effects against cancer, inflammation, and oxidative stress, with breast, colon, colorectal, pancreatic, and prostate cancers the most frequently studied types.
The research also identified Sabinsa’s Curcumin C3 Complex® as the most clinically studied curcumin brand. To quote the authors “By analyzing the studies describing clinical trial studies of curcumin, we found that oral curcumin (C3 complex) was a popular theme. Indeed, the C3 complex used in these studies is a standardized extract of dried rhizomes of C. longa and it represents the most clinically studied form of curcumin, evaluated in clinical trials in the context of cancer, but also in multiple other conditions, including Alzheimer’s disease, psoriasis vulgaris, oral lichen planus, osteoarthritis, inflammation associated with metabolic syndrome and obesity, radiation dermatitis, as well as for modulation of human gut microbiome.”.
Abstract: The current study aimed to provide a comprehensive bibliometric overview of the literature on curcumin, complementing the previous reviews and meta-analyses on its potential health benefits. Bibliometric data for the current analysis were extracted from the Web of Science Core Collection database, using the search string TOPIC=(“curcumin*”), and analyzed by the VOSviewer software. The search yielded 18,036 manuscripts. The ratio of original articles to reviews was 10.4:1. More than half of the papers have been published since 2014. The major contributing countries were the United States, China, India, Japan, and South Korea. These publications were mainly published in journals representing the following scientific disciplines: biochemistry, chemistry, oncology, and pharmacology. There was a significant positive correlation between the total publication count and averaged citations per manuscript for affiliations, but not for countries/regions and journals. Chemicals that were frequently mentioned in the keywords of evaluated curcumin publications included curcuminoids, resveratrol, chitosan, flavonoids, quercetin, and polyphenols. The literature mainly focused on curcumin’s effects against cancer, inflammation, and oxidative stress. Cancer types most frequently investigated were breast, colon, colorectal, pancreatic, and prostate cancers.
Keywords: curcumin; pharmacology; bibliometrics; biochemistry; cancer; citation analysis; VOSviewer; Web of Science
Curcumin: Total-Scale Analysis of the Scientific Literature, Atanas G. Atanasov et al, journal, Molecules (2019, 24, 1393)

Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa) that has been associated with antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial activities as indicated by over 6,000 citations. In addition, over one hundred clinical studies have been carried out with curcumin. One of the major problems with curcumin is perceived to be the bioavailability. How curcumin should be delivered in vivo, how bioavailable is it, how well curcumin is absorbed and how it is metabolized, is the focus of this review. Various formulations of curcumin that are currently available are also discussed.
Curcumin / Piperine : Besides these natural compounds have been also used to increase the bioavailability of curcumin. One of them is piperine, a major component of black pepper, known as inhibitor of hepatic and intestinal glucuronidation and is also shown to increase the bioavailability of curcumin. This effect of piperine on the pharmacokinetics of curcumin has been shown to be much greater in humans than in rats. In humans, curcumin bioavailability was increased by 2,000% at 45 minutes after co-administering curcumin orally with piperine, whereas in rats, it has been found that concomitant administration of piperine 20 mg/kg with curcumin 2 g/kg increased the serum concentration of curcumin by 154% for a short period of 1-2 hours post drug. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects
Key words : Curcumin, Nano-formulation, Biological availability, Metabolism, Anticancer
Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: the Golden Pigment from Golden Spice, Cancer Res Treat. 2014;46(1): 2-18

Background : Dietary bioactive compounds capable of improving metabolic profiles would be of great value, especially for overweight individuals undergoing a caloric restriction (CR) regimen. Curcumin (Cur), a possible anti-obesity compound, and piperine (Pip), a plausible enhancer of Cur’s bioavailability and efficacy, may be candidate agents for controlling body fat, metabolism and low grade inflammation.
Methods : 47 eight-week-old male C57BL/6 mice were fed a high fat diet (HFD) for 23 weeks to induce obesity. Then, mice were divided into 5 groups. Group 1 continued on HFD ad libitum. The other 4 groups underwent CR (reduced 10% HFD intake for 10 weeks, 20% for 20 weeks) with Cur, Pip, Cur + Pip or none of these. Percent body fat, plasma inflammatory markers associated with obesity (interferon (IFN)-γ, interleukin (IL)-10, IL-12 p70, IL-1β, IL-6 and KC/GRO), plasma Cur metabolites and liver telomere length were measured.
Results : Compared to the other groups, obese mice who underwent CR and received Cur + Pip in their diet lost more fat and had significantly lower IL-1β and KC/GRO. Tandem mass spectrometry analysis of plasma from obese mice under CR showed no difference in Cur metabolite levels between groups supplemented with Cur alone or combined with Pip. However, plasma IL-1β levels were inversely correlated with curcumin glucuronide. Minor modulation of telomere length were observed.
Conclusions : It is plausible that supplementing the high fat diet of CR mice with Cur + Pip may increase loss of body fat and suppresses HFD induced inflammation. Combination of Cur and Pip has potential to enhance CR effects for the prevention of metabolic syndrome.
Curcumin and piperine supplementation of obese mice under caloric restriction modulates body fat and interleukin - Nutrition Metabolism - Taiki Miyazawa, Kiyotaka Nakagawa, Sharon H. Kim, Michael J. Thomas, Ligi Paul, Jean-Marc Zingg, Gregory G. Dolnikowski, Susan B. Roberts, Fumiko Kimura, Teruo Miyazawa, Angelo Azzi and Mohsen Meydani - Miyazawa et al. Nutrition & Metabolism (2018) 15:12

ABSTRACT. Oxidative stress plays a key role in the development of chronic pulmonary complications of sulfur mustard (SM). Curcuminoids are polyphenols with documented safety and antioxidant activity. The present study aimed to investigate the efficacy of short-term supplementation with curcuminoids (co-administered with piperine to enhance the bioavailability of curcuminoids) in alleviating systemic oxidative stress and clinical symptoms, and improvement of health-related quality of life (HRQoL) in subjects suffering from chronic pulmonary complications due to SM exposure who are receiving standard respiratory treatments. Eighty-nine subjects were recruited to this randomized double-blind placebo-controlled trial, being randomly allocated to either curcuminoids (1500 mg/day) + piperine (15 mg/day) combination (n = 45) or placebo (n = 44) for a period of 4 weeks. High-resolution computed tomography suggested the diagnosis of bronchiolitis obliterans in all subjects. Efficacy measures were changes in serum levels of reduced glutathione (GSH) and malonedialdehyde (MDA). The severity and frequency of respiratory symptoms and HRQoL were also assessed using St. George respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) indices. Serum levels of GSH were increased whilst those of MDA decreased by the end of trial in both groups. Likewise, there were significant improvements in the total as well as subscale (symptoms, activity and impact) SGRQ and CAT scores in both groups. However, comparison of magnitude of changes revealed a greater effect of curcuminoids-piperine combination compared to placebo in elevating GSH, reducingMDA and improving CAT and SGRQ (total and subscale) scores (p max 0.001). Regarding the promising effects of curcuminoids on the measures of systemic oxidative stress, clinical symptoms and HRQoL, these phytochemicals may be used as safe adjuvants in patients suffering from chronic SM-induced pulmonary complications who are receiving standard treatments.
Discussion : In summary, the present study provides the first clinical evidence on the benefits of short-term adjunctive therapy with curcuminoids–piperine combination in suppressing systemic oxidative stress, decreasing symptoms and improving the HRQoL of patients suffering from chronic SM-induced pulmonary complications. This finding becomes more important when considering the fact that treatment options for mustard lung that are currently in practice are very limited and mainly symptomatic, including inhaled corticosteroids and broncholdilators (mainly longacting β-agonists). Current data suggests that these phytochemicals might be a useful addition to the armamentarium against chronic SM-induced complications, and encourage further research to explore the impact of curcuminoids on proininflammatory biomarkers and additional oxidative stress biomarkers (e.g., F2 isoprostanes and superoxide dismutase) in serum, bronchoalveolar lavage fluid, and saliva.
KEYWORDS. antioxidant, lipid peroxidation, lung, mustard gas, randomized controlled trial
Effects of Curcuminoids-Piperine Combination on Systemic Oxidative Stress, Clinical Symptoms and Quality of Life in Subjects with Chronic Pulmonary Complications Due to Sulfur Mustard: A Randomized Controlled Trial - Yunes Panahi, Mostafa Ghanei, Ali Hajhashemi and Amirhossein Sahebkar - Journal of Dietary Supplements, Early Online:1–13, 2014 C

Abstract : Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant of the ginger family, has been used for the treatment of diabetes in Ayurvedic and traditional Chinese medicine. The active component of turmeric, curcumin, has caught attention as a potential treatment for diabetes and its complications primarily because it is a relatively safe and inexpensive drug that reduces glycemia and hyperlipidemia in rodent models of diabetes. Here, we review the recent literature on the applications of curcumin for glycemia and diabetes-related liver disorders, adipocyte dysfunction, neuropathy, nephropathy, vascular diseases, pancreatic disorders, and other complications, and we also discuss its antioxidant and anti-inflammatory properties. The applications of additional curcuminoid compounds for diabetes prevention and treatment are also included in this paper. Finally, we mention the approaches that are currently being sought to generate a “super curcumin” through improvement of the bioavailability to bring this promising natural product to the forefront of diabetes therapeutics.
Conclusion : Recent research has provided the scientific basis for “traditional” curcumin and confirmed the important role of curcumin in the prevention and treatment of diabetes and its associated disorders. Curcumin could favorably affect most of the leading aspects of diabetes, including insulin resistance, hyperglycemia, hyperlipidemia, and islet apoptosis and necrosis (Figure 2). In addition, curcumin could prevent the deleterious complications of diabetes. Despite the potential tremendous benefits of this multifaceted nature product, results from clinical trials of curcumin are only available in using curcumin to treat diabetic nephropathy, microangiopathy and retinopathy so far. Studies are badly needed to be done in humans to confirm the potential of curcumin in limitation of diabetes and other associated disorders. Further, multiple approaches are also needed to overcome limited solubility and poor bioavailability of curcumin. These include synthesis of curcuminoids and development of novel formulations of curcumin, such as nanoparticles, liposomal encapsulation, emulsions, and sustained released tablets. Enhanced bioavailability and convinced clinical trial results of curcumin are likely to bring this promising natural product to the forefront of therapeutic agents for diabetes by generating a “super curcumin” in the near future.
Curcumin and Diabetes: A Systematic Review, Dong-wei Zhang, Min Fu, Si-Hua Gao, and Jun-Li Liu, Evidence-Based Complementary and Alternative Medicine Volume 2013, Article ID 636053, 16 pages

Dietary deficiency of docosahexaenoic acid (C22: 6n-3; DHA) is linked to the neuropathology of several cognitive disorders, including anxiety. DHA, which is essential for brain development and protection, is primarily obtained through the diet or synthesized from dietary precursors, however the conversion efficiency is low. Curcumin (diferuloylmethane), which is a principal component of the spice turmeric, complements the action of DHA in the brain, and this study was performed to determine molecular mechanisms involved. We report that curcumin enhances the synthesis of DHA from its precursor, α-linolenic acid (C18: 3n-3; ALA) and elevates levels of enzymes involved in the synthesis of DHA such as FADS2 and elongase 2 in both liver and brain tissue. Furthermore, in vivo treatment with curcumin and ALA reduced anxiety-like behavior in rodents. Taken together, these data suggest that curcumin enhances DHA synthesis, resulting in elevated brain DHA content. These findings have important implications for human health and the prevention of cognitive disease, particularly for populations eating a plant-based diet or who do not consume fish, a primary source of DHA, since DHA is essential for brain function and its deficiency is implicated in many types of neurological disorders.
Conclusion : The n-3 fatty acids DHA and EPA are essential for human health that are obtained through dietary animal sources or synthesized from precursors. We provide evidence that curcumin enhances the biosynthesis of hepatic DHA from n-3 precursors and enhances DHA accretion in the brain. These data provide a novel insight into a potential mechanism by which curcumin ameliorates neurocognitive disease.
Keywords : DHA synthesis; Curcumin; ALA; DPA; omega 3 fatty acids; docosahexaenoic acid
Curcumin boosts DHA in the brain: implications for the prevention of anxiety disorders, Biochim Biophys Acta. 2015 May ; 1852(5): 951–961. doi:10.1016/ j.bbadis. 2014.12.005, Aiguo Wu, Emily E. Noble, Ethika Tyagi, Zhe Ying, Yumei Zhuang

Several compounds extracted from spices and herbs exhibit antiviral effects in vitro, suggesting potential pharmacological uses. Curcumin, a component of turmeric, has been used as a food additive and herbal supplement due to its potential medicinal properties. Previously, curcumin exhibited antiviral properties against several viruses, including dengue virus and hepatitis C virus, among others. Here, we describe the antiviral effect of curcumin on Zika and chikungunya viruses, two mosquito-borne outbreak viruses. Both viruses responded to treatment of cells with up to 5 mM curumin without impacting cellular viability.We observed that direct treatment of virus with curcumin reduced infectivity of virus in a dose- and timedependent manner for these enveloped viruses, as well as vesicular stomatitis virus. In contrast, we found no change in infectivity for Coxsackievirus B3, a non-enveloped virus. Derivatives of curcumin also exhibited antiviral activity against enveloped viruses. Further examination revealed that curcumin interfered with the binding of the enveloped viruses to cells in a dose-dependent manner, though the integrity of the viral RNA was maintained. Together, these results expand the family of viruses sensitive to curcumin and provide a mechanism of action for curcumin's effect on these enveloped viruses.
The ability of curcumin to prevent viral replication strongly suggests that this molecule and its derivatives may hold promise for the development of broad-range antivirals. Curcumin in the human diet, further, could provide a simple means to prevent infection by enveloped viruses.
Keywords: Curcumin Enveloped virus Viral binding
Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding - Bryan C. Mounce, Teresa Cesaro, Lucia Carrau, Thomas Vallet, Marco Vignuzzi - Antiviral Research 142 (2017)

Abstract Background: The dietary spice Curcuma longa, also known as turmeric, has various biological effects. Both a water extract and a supercritical carbon dioxide extract of C. longa showed anti-inflammatory activities in animal studies. However, the anti-inflammatory effect in humans of a mixture of these two C. longa extracts (CLE) is poorly understood. Therefore, we investigated the effect of CLE containing anti-inflammatory turmeronols on chronic inflammation and general health.
Methods: We performed a randomized, double-blind, placebo-controlled study in healthy subjects aged 50 to 69 years with overweight. Participants took two capsules containing CLE (CLE group, n = 45) or two placebo capsules (placebo group, n = 45) daily for 12 weeks, and serum inflammatory markers were measured. Participants also completed two questionnaires: the Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey (SF-36) and the Profile of Mood States (POMS) scale. Treatment effects were analyzed by two way analysis of variance followed by a t test (significance level, p max 0.05).
Results: After the intervention, the CLE group had a significantly lower body weight (p max 0.05) and body mass index (p max 0.05) than the placebo group and significantly lower serum levels of C-reactive protein (p max 0.05) and complement component 3 (p max 0.05). In addition, the CLE group showed significant improvement of the MOS SF-36 mental health score (p max 0.05) and POMS anger-hostility score (p max 0.05).
Conclusion: CLE may ameliorate chronic low-grade inflammation and thus help to improve mental health and mood disturbance.
Discussion : Compared with the placebo group, body weight, BMI, and serum levels of CRP and C3 were significantly lower in the CLE group. In addition, the CLE group showed a significant improvement in the SF-36 subscale score for mental health and the POMS score for anger and hostility. These results suggest that intake of a mixture of a hot water extract and supercritical carbon dioxide extract of C. longa may have the potential to improve mental health and negative mood state by reducing chronic low-grade inflammation.
Curcuma longa extract improves serum inflammatory markers and mental health in healthy participants who are overweight: a randomized, double-blind, placebo-controlled trial Ryusei Uchio , Kengo Kawasaki, Chinatsu Okuda‑Hanafusa, Ryosuke Saji, Koutarou Muroyama, Shinji Murosaki, Yoshihiro Yamamoto and Yoshitaka Hirose

ABSTRACT : Endurance running training can lead to gradual accumulation of inflammation and soreness ultimately resulting in overuse injuries. Management of soreness and inflammation with pharmaceuticals (i.e. non-prescription pain relievers) during long-term training is not a suitable solution due to known side effects (e.g. gastrointestinal complications, etc.). Dietary polyphenols (i.e. curcumin, pomegranate, etc.) have been purported to reduce inflammation and muscle sore-ness, without these negative side effects making them ideal for use in an exercise model. The purpose of the present feasibility study was to explore the combined effect of optimized curcumin and pomegranate extract supplementation prior to (PRE) and after (4H and 24H) an organized half-marathon race on blood inflammatory proteins and inflammation-associated RNA. Daily supplementation (1000 mg/d) started 26 days before a half-marathon which doubled on days 27-31. Data were analyzed with R software and Welch t-test, significance set at p max 0.05. At both 4H and 24H, supplementation was associated with alterations in protein (IL-10, IL-13, IL-4, ITAC, MIP-1alpha, MIP-3alpha, BDNF, sIL-2Ralpha, and TNF-alpha; p max 0.05) and RNA (CCL22, GUSB, IL-6, LINC00305, NKILA, PTGES, THRIL, TRAF6, ARG2, CD1A, CD55, CFI, CSF2, CXC3CL1, CX3CR1, EDNRB, GATA3, LILRB5, THY1, CD3D, MRC1, GPR183, HAMP, MBL2, CASP3, B2M, KLRF2, PDCD1LG2, IL-10, PTGS2, TLR2, IL-6R, IL-8, IL-7R, MASP1, MYD88, TNFRSF1B, TNFRSF1A, and TIRAP; p max 0.05) biomarkers com-pared to control. Pathway classification of these biomarkers indicated supplementation may be associated with a more favorable muscle recovery profile. Our findings support the notion that combined cur-cumin and pomegranate supplementation may represent a useful addition to a comprehensive exercise training plan.
Study for Curcumin + Pomegranate
Conclusion : Our findings support the notion that combined curcumin and pomegranate supplementation may represent a useful addition to a comprehensive exercise training plan. In conclusion, it is well documented that reduced post-exercise inflammation is associated with a faster return to normal function in activities of daily living or training The key findings of the present study when subjects were supplemented is consistent with previously reported reductions in post-exercise inflammation with curcumin alone Additionally, previous research with resistance training has shown an improvement in muscle damage with the consumption of pomegranate juice that is in line with the results of the current study it is reasonable to speculate that combined supplementation with optimized curcumin and pomegranate extract may be useful as part of a comprehensive plan designed to mitigate post-exercise inflammation/injury and improve subsequent recovery between sessions.
Additional research in this area of study is warranted to further characterize additional supplementation strategies (i.e. flexible dosing, short-term dosing, etc.) and methods for incorporating combined curcumin and pomegranate supplementation into individualized training plans.
Alterations in Systemic Inflammatory Response Following a Half-Marathon Race with a Combined Curcumin and Pomegranate Supplement: A Feasibility Study - Elizabeth A. Tanner , Melody A. Gary , Asheal A. Davis , Stephan Michalik & Brian K. McFarlin

Abstract : Diabetes mellitus (DM) is an ensemble of metabolic conditions that have reached pandemic proportions worldwide. Pathology’s multifactorial nature makes patient management, including lifelong drug therapy and lifestyle modification, extremely challenging. Currently, there is growing evidence about the effectiveness of using herbal supplements in preventing and controlling DM. Curcumin is a bioactive component found Curcuma longa, which exhibits several physiological and pharmacological properties such as antioxidant, anti-inflammatory, anticancer, neuroprotective, and anti-diabetic activities. For these reasons, our objective is to systematically review the effects of Curcuma longa or curcumin on DM. Databases such as PUBMED and EMBASE were searched, and the final selection included sixteen studies that fulfilled the inclusion criteria. The results showed that curcumin’s anti-diabetic activity might be due to its capacity to suppress oxidative stress and inflammatory process. Also, it significantly reduces fasting blood glucose, glycated hemoglobin, and body mass index. Nanocurcumin is also associated with a significant reduction in triglycerides, VLDL-c, total cholesterol, LDL-c, HDL-c, serum C reactive protein, and plasma malonaldehyde. Therefore, it can be considered in the therapeutic approach of patients with DM.
Conclusion : T2DM has a multifactorial pathology and affects thousands of people worldwide. Its treatment consists of lifestyle changes, diet, physical activity, and therapies with medications for the rest of life. Curcumin is a natural anti-inflammatory and anti-diabetic agent representing a safe and low-cost alternative for this condition’s therapeutic approach, although it is still necessary to know its effective dose. We suggest that more robust and rigorous randomized controlled clinical trials are carried out to establish the role of curcumin in the therapeutics of T2DM.
Keywords: Curcuma longa, curcumin, curcuminoids, diabetes, type 2 diabetes mellitus
The Effects of Curcumin on Diabetes Mellitus: A Systematic Review, Ledyane Taynara Marton, Laís Maria Pescinini-E-Salzedas, Maria Eduarda Côrtes Camargo, Sandra M Barbalho, Jesselina F Dos Santos Haber, Renata Vargas Sinatora, Claudia Rucco Penteado Detregiachi, Raul J S Girio, Daniela Vieira Buchaim, Patricia Cincotto Dos Santos Bueno, Front Endocrinol (Lausanne), 2021 May 3

Infection with the HCV is one of the major causes of chronic liver disease with an estimated 184 million persons worldwide positive for HCV antibodies and 4 million newly infected each year. The situation is worrying in emerging countries of Central and Southeast Asia, North Africa and Middle East with seroprevalence around 3%–5%. Central Africa and Egypt remain regions of very high endemicity with a 25% prevalence in the latter. Hepatitis C is therefore a global health problem with striking inequalities in the access to healthcare and implementation of treatments between world regions.
(...) Several aspects of this study deserve attention. Curcumin is inexpensive, efficiently blocks HCVentry into hepatocytes, exerts pan-genotypic antiviral activity and can be orally administered and preliminary data from Anggakusuma et al seem to indicate a high barrier to resistance. Recent clinical trials have pointed its high tolerance and favourable safety profile in healthy subjects.10 Curcumin is combinable with existing therapies,9 and may be judiciously combined to per os IFN-free therapies currently under trials, based upon novel pan-genotypic DAA. (...)
Comments for Curcumin
Curcumin against hepatitis C virus infection: spicing up antiviral therapies with ‘nutraceuticals’ - Eve-Isabelle Pécheur, Gut July 2014 Vol 63 No 7

The dengue virus is considered to be a globally important human pathogen prevalent in tropical and subtropical regions of the world. According to a recent estimate, the disease burden due to DENV infections is ∼390 million infections per year globally in ∼100 countries including the southern US, Puerto Rico and Hawaii, resulting in nearly ∼25,000 deaths mostly among children. Despite the significant morbidity and mortality that results from DENV infections, there is currently no effective chemotherapeutic treatment for DENV infections. We identified curcumin as an inhibitor of DENV2 NS2B/NS3protease in a previous high-throughput screening (HTS) campaign. We synthesized four analogues of curcumin (curcuminoids) and tested the in vitro protease inhibition activity and inhibition of replication by cell-based assays. The results revealed that curcumin is a weak inhibitor of the viral protease. However, the analogues exhibited more potent inhibition of DENV infectivity in plaque assays suggesting that the cellular pathway(s) required for viral replication and/or assembly are targeted by these compounds. Further analysis shows that inhibition of genes involved in lipid biosynthesis, and of actin polymerization by curcuminoids, are likely to be involved as their mode of action in DENV2-infected cells. Three of the curcumin derivatives possess good selectivity indices (SI) ( min 10) when compared to the parent curcumin.
Conclusion : We conclude that curcuminoids exhibit their anti-viral activities through a variety of ways on the host cells, but with modest effect in DENV protease. Modulation of host actin and lipids may be involved in regulating the viral binding and entry. Recent studies on DENV mouse models indicated that curcumin treatment reduced the DENV viremia effectively (Ichsyani et al., 2017) indicating that these analogues might be promising in antiviral therapy against DENV.
Inhibition of dengue virus by curcuminoids - Anuradha Balasubramanian, Rajendra Pilankatta, Tadahisa Teramoto, Ayyiliath M. Sajith, Evaristus Nwulia, Amol Kulkarni, Radhakrishnan Padmanabhan - Antiviral Research 162 (2019) 71–78

In vitro and pre-clinical studies have suggested that addition of the diet-derived agent curcumin may provide a suitable adjunct to enhance efficacy of chemotherapy in models of colorectal cancer. However, the majority of evidence for this currently derives from established cell lines.
Here, we utilised patient-derived colorectal liver metastases (CRLM) to assess whether curcumin may provide added benefit over 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) in cancer stem cell (CSC) models.
Combination of curcumin with FOLFOX chemotherapy was then assessed clinically in a phase I dose escalation study. Curcumin alone and in combination significantly reduced spheroid number in CRLM CSC models, and decreased the number of cells with high aldehyde dehydrogenase activity (ALDHhigh/ CD133−). Addition of curcumin to oxaliplatin/5-FU enhanced anti-proliferative and pro-apoptotic effects in a proportion of patient-derived explants, whilst reducing expression of stem cell-associated markers ALDH and CD133. The phase I dose escalation study revealed curcumin to be a safe and tolerable adjunct to FOLFOX chemotherapy in patients with CRLM (n = 12) at doses up to 2 grams daily.
Curcumin may provide added benefit in subsets of patients when administered with FOLFOX, and is a well-tolerated chemotherapy adjunct.
Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy Cancer Letters 364 (2015) 135–141

Objective: To assess the efficacy and safety of Curcuma longa Extract and curcumin supplements on osteoarthritis (OA).
Methods: The databases such as Pubmed and Cochrane Library were searched to collect the article about Curcuma longa Extract and curcumin in the treatment of OA. Then, randomized controlled trials (RCTs) were selected and their data was extracted. Finally, the RevMan5.3 was utilized for risk of bias assessment and meta-analysis, the STATA15.0 were utilized for publication bias assessment, and GRADE tool were used for the evidence quality assessment of primary outcomes.
Results: A total of 15 RCTs involving 1621 participants were included. (1) Compared with placebo, Curcuma longa Extract and curcumin (C.) can decrease the VAS and WOMAC score-pain, the WOMAC score-function and the WOMAC score-stiffness. In terms of adverse events, Curcuma longa Extract and curcumin are comparable to those of placebo. (2) Compared with NSAIDs, Curcuma longa Extract and curcumin have similar effects on joint pain, function and stiffness. The incidence of adverse events in Curcuma longa Extract and curcumin was lower. (3) Compared with the NSAIDs group, C.+NSAIDs can also decrease the VAS and WOMAC score-pain, the WOMAC score-function and the WOMAC score-stiffness. In terms of adverse events, the addition of Curcuma longa Extract and curcumin to NSAIDs did not increase adverse events.
So, Results showed significant effects of supplementations on the VAS and WOMAC score-pain, the WOMAC score-function and the WOMAC score-stiffness.
Conclusion: Curcuma longa Extract and curcumin may be a safer and effective supplement for OA patients. It is recommended to use Curcuma longa Extract and curcumin supplement for OA patients for more than 12 weeks.
Keywords: Curcuma longa Extract; Curcumin; Meta-analysis; Osteoarthritis; Systematic review.
The efficacy and safety of Curcuma longa Extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis, Liuting Zeng, Kailin Yang, Wensa Hao, Ganpeng Yu, Hua Chen, Biosci Rep, 2021 May 21

Abstract. Background: The terminal stage of Ebola and other viral diseases is often the onset of a cytokine storm, the massive overproduction of cytokines by the body’s immune system. Materials and Methods: The actions of curcumin in suppressing cytokine release and cytokine storm are discussed. Results: Curcumin blocks cytokine release, most importantly the key pro-inflammatory cytokines, interleukin- 1, interleukin-6 and tumor necrosis factor-α. The suppression of cytokine release by curcumin correlates with clinical improvement in experimental models of disease conditions where a cytokine storm plays a significant role in mortality. Conclusion: The use of curcumin should be investigated in patients with Ebola and cytokine storm. Intravenous formulations may allow achievement of therapeutic blood levels of curcumin
Conclusion : The activity of curcumin in suppressing multiple cytokines, and its activity in experimental models of diseases and conditions associated with cytokine storm, suggest it may be useful in the treatment of patients with Ebola and cytokine storm. Curcumin is poorly absorbed from the intestinal tract; however, intravenous formulations may allow therapeutic blood levels of curcumin to be achieved in patients diagnosed with cytokine storm. Clinical status and levels of important cytokines, such as IL1β, IL6 and TNFα, should be monitored carefully when patients are treated with curcumin.
Key Words: Curcumin, cytokine storm, Ebola, interleukin-1, interleukin-6, tumor necrosis factor-α, review.,virus
Curcumin Suppression of Cytokine Release and Cytokine Storm. A Potential Therapy for Patients with Ebola and Other Severe Viral Infections - PETER P. SORDILLO and LAWRENCE HELSON - in vivo 29: 1-4 (2015)

Oxidative stress, Nrf2-HO-1 and TLR-MAPK/NF-κB signaling pathways have been proved to be involved in influenza A virus (IAV) replication and influenzal pneumonia. In the previous studies, we have performed several high-throughput drug screenings based on the TLR pathways. In the present study, through plaque inhibition test, luciferase reporter assay, TCID50, qRT-PCR, western blotting, ELISA and siRNA assays, we investigated the effect and mechanism of action of curcumin against IAV infection in vitro and in vivo. The results showed that curcumin could directly inactivate IAV, blocked IAV adsorption and inhibited IAV proliferation. As for the underlying mechanisms, we found that curcumin could significantly inhibit IAV-induced oxidative stress, increased Nrf2, HO-1, NQO1, GSTA3 and IFN-β production, and suppressed IAV-induced activation of TLR2/4/7, Akt, p38/JNK MAPK and NF-κB pathways. Suppression of Nrf2 via siRNA significantly abolished the stimulatory effect of curcumin on HO-1, NQO1, GSTA3 and IFN-β production and meanwhile blocked the inhibitory effect of curcumin on IAV M2 production. Oxidant H2O2 and TLR2/4, p38/JNK and NF-κB agonists could significantly antagonize the anti-IAV activity of curcumin in vitro. Additionally, curcumin significantly increased the survival rate of mice, reduced lung index, inflammatory cytokines and lung IAV titer, and finally improved pulmonary histopathological changes after IAV infection. In conclusion, curcumin can directly inactivate IAV, inhibits IAV adsorption and replication; and its inhibition on IAV replication may be via activating Nrf2 signal and inhibiting IAV-induced activation of TLR2/4, p38/JNK MAPK and NF-κB pathways.
In conclusion, besides directly inactivating IAV and inhibiting IAV adsorption, curcumin can activate Nrf2 signal, stimulates the production of many antioxidases, such as CAT, SOD, GSH-Px, HO-1, NQO1 and GSTA3, suppresses IAV-mediated oxidative stress and further indirectly inhibits IAV-induced activation of TLR2/4, p38/JNK MAPK and NF-κB pathways, which may inhibit both IAV-mediated inflammation and IAV replication. Meanwhile, activation of Nrf2-HO-1 pathway can increase the production of IFN-β which may also further suppress IAV replication. Finally curcumin improves IAV-induced ALI/ARDS (Fig. 8). Additionally, curcumin has been used as a coloring agent and spice in foods for thousands of years, it possesses very low cytotoxicity, this may make curcumin to be utilized to treat IAV infection in the clinic directly.
Inhibition of curcumin on influenza A virus infection and influenzal pneumonia via oxidative stress, TLR2/4, p38/JNK MAPK and NF-κB pathways - Jianping Dai, Liming Gu, Yun Su, Qianwen Wang, Ying Zhao, Xiaoxua Chen, Huixiong Deng, Weizhong Li, Gefei Wang, Kangsheng Li - International Immunopharmacology 54 (2018) 177–187

Earlier this month, Sami Labs filed criminal complaint against Bayir Extracts for allegedly supplying adulterated Turmeric Oleoresin with a forged Certificate of Analysis. This impounding of evidence is part of the resulting investigation.
The samples turned over to the police included the controversial Curcumin batches Sami purchased from Bayir. It may be noted that these were the same samples reported as being contaminated with fossil fuels, causing the product to be partially synthetic and not natural as it was claimed in their Certificate of Analysis.
Results of radiocarbon testing by University of Georgia Center for Applied Isotope Studies determined that commercially available samples of Curcumin sold by Bayir Extracts was 43% synthetic. Further analysis of three additional batches of Bayir’s Curcumin material have been released by the University of Georgia’s Center for Applied Isotope Studies, and they are the following:
Batch: BE/CUR/14015 - 32% synthetic
Batch: BE/CUR/P/14016 - 43% synthetic
Batch: BE/CUR/14017 Totally natural
Batch: BE/CUR/14018 - 45% synthetic
“It’s interesting to note one of the four batches was natural curcumin, but the truth is that three batches are synthetic,” said Sabinsa founder Dr. Muhammed Majeed. “Additionally, when we alerted the industry to the legal action against Bayir initiated in India, their response was to file a gag order against us. However, we are not stating anything that is derogatory, false, defamatory or untrue, but will be proven in a court of law.”