The Effects of Curcumin Plus Piperine Co-administration on Inflammation and Oxidative Stress: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The beneficial effects of curcumin against various chronic disorders have been shown in the last few decades. However, due to its low bioavailability, therapeutic effects are less than expected. Piperine has been used in scientific evaluations as an effective compound to increase the bioavailability of curcumin. The present review investigated the impact of curcumin plus piperine intake on oxidative stress and inflammatory markers of Randomized Clinical Trials (RCTs). METHODS: Using relevant keywords, we searched Cochrane Library, Scopus, PubMed, and Web of Science between January 1st, 1970, and September 30th, 2022. A comprehensive search for RCTs was performed. Continuous data were pooled by Standard Mean Difference (SMD) and 95% confidence interval. All related statistical analyses were performed using Comprehensive Meta-Analysis (CMA) software. RESULTS: A total of 13 articles were incorporated into the final meta-analysis. According to the current meta-analysis, curcumin plus piperine administration showed a significantly increased SOD activity and GSH levels while significantly decreased MDA concentrations. In addition, our study revealed that curcumin plus piperine significantly decreased TNF-α and IL-6 concentrations. CONCLUSION: These results indicated that curcumin plus piperine administration could effectively reduce oxidative stress and inflammation.

Subjective biosafety assessment of bisdemethoxycurcumin from the rhizomes of Curcuma longa.

Introduction/Background: Curcuma longa, a plant native to the Indian subcontinent has a variety of biological activities. Curcumin is the most abundant and biologically active compound with many therapeutic properties. Demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) - the two other bioactive components present in Curcuma longa, besides curcumin, are collectively termed curcuminoids. Apart from the well-known curcumin, BDMC also has been reported to possess promising biological and pharmacological effects, but very little scientific evidence on its safety assessment has been published.Objective: The present study was undertaken to determine the safety of pure BDMC from Curcuma longa extract in rodents which comprises of general toxicity (both four weeks and three months duration), reproductive/developmental toxicity and genotoxicity studies.Methods: The Good Laboratory Practice studies were carried out in accordance with the test guidelines established by the Organization for Economic Cooperation and Development.Results: No treatment-related adverse findings were seen in general toxicity testing and a no observed adverse effect level (NOAEL) of 1000 mg/kg/day was established after four weeks (sub-acute) and three-months (sub-chronic) dosing. Evaluation of fertility, embryo-fetal, and post-natal reproductive and developmental parameters also showed no adverse findings with a NOAEL of 1000 mg/kg/day established. The results of genotoxicity as evaluated by in vitro reverse mutation assay, and in vivo micronucleus test in mice indicate that BDMC did not induce any genotoxic effects.Conclusion: Oral administration of BDMC is safe in rodents and non-mutagenic, with no adverse effects under experimental conditions.

The effects of curcumin-piperine supplementation on inflammatory, oxidative stress and metabolic indices in patients with ischemic stroke in the rehabilitation phase: a randomized controlled trial.

BACKGROUND: Stroke is a leading cause of death worldwide, which is associated with a heavy economic and social burden. The purpose of this study was to investigate the effects of supplementation with curcumin-piperine combination in patients with ischemic stroke in the rehabilitation stage. METHODS: In this randomized controlled trial, 66 patients with stroke were randomized into two groups receiving curcumin-piperine tablets (500 mg curcumin + 5 mg piperine) and matched placebo tablets for 12 weeks. High-sensitivity C-reactive protein (hs-CRP), carotid intima-media thickness (CIMT), thrombosis, total antioxidant capacity (TAC), lipid profile, anthropometric indices, blood pressure, and quality of life were assessed before and after the intervention. Statistical data analysis was done using SPSS22 software. RESULTS: A total of 56 patients with a mean age of 59.80 ± 4.25 years completed the trial. Based on ANCOVA test, adjusted for baseline values, curcumin-piperine supplementation for 12 weeks resulted in significant reductions in serum levels of hs-CRP (p = 0.026), total cholesterol (TC) (p = 0.009), triglycerides (TG) (p = 0.001), CIMT (p = 0.002), weight (P = 0.001), waist circumference (p = 0.024), and systolic and diastolic blood pressure (p < 0.001), and a significant increase in TAC (p < 0.001) in comparison to the placebo. Pain score significantly increased in both groups; however, its increase was significantly higher in the placebo group compared with the intervention group (p = 0.007). No significant changes were observed between the two groups in terms of serum fibrinogen, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and quality of life indices. CONCLUSION: Curcumin-piperine supplementation had beneficial effects on CIMT, serum hs-CRP, TC, TG, TAC, and systolic and diastolic blood pressure in patients with ischemic stroke in the rehabilitation stage.

Assessment of Safety Profile of Activated Curcumin C3 Complex (AC3®), Enriched Extract of Bisdemethoxycurcumin from the Rhizomes of Curcuma longa.

The present work was carried out to investigate the toxic effects of Activated Curcumin C3 Complex (AC3®) through the methods of acute, subacute, subchronic, reproductive/developmental toxicity, and genotoxicity when administered orally in experimental rodents. The studies were carried out in line with OECD principles of good laboratory practice. A single-dose acute oral toxicity study was conducted on female Wistar rats that produced no toxic effects after 14 days (the observation period) of treatment. Subacute, subchronic, and reproductive/developmental studies were conducted in Wistar rats, divided equally into vehicle control, 125, 250, and 500 mg/kg dose groups along with recovery groups for vehicle control and high dose. In all the studies, there were no abnormal clinical signs/behavioral changes, reproductive and developmental parameters, or gross and histopathological changes. Likewise, no alteration was found in the body weight, hematology, and other biochemical parameters. Also, it did not show mutagenicity in the in vitro AMES test or clastogenicity and aneugenicity in the in vivo micronucleus test, indicating that AC3® did not induce any genotoxic effects. This revealed that oral administration of AC3® is safe in rodents, nonmutagenic, and had no observed adverse effects under experimental conditions.

The Effects of Antioxidants and Pulsed Magnetic Fields on Slow and Fast Skeletal Muscle Atrophy Induced by Streptozotocin: A Preclinical Study.

Results: Our findings suggest that antioxidants and PMF may alleviate impaired protein synthesis and degradation pathways in skeletal muscle atrophy. PTS showed a positive effect on the anabolic pathway, while RSV and PMF demonstrated potential for ameliorating the catabolic pathway. Notably, the combination therapy of antioxidants and PMF exhibited a stronger ameliorative effect on skeletal muscle atrophy than either intervention alone. Conclusion: The present results highlight the benefits of employing a multimodal approach, involving both antioxidant and PMF therapy, for the management of muscle-wasting conditions. These treatments may have potential therapeutic implications for skeletal muscle atrophy.

A Standardized Withania somnifera (Linn.) Root Extract with Piperine Alleviates the Symptoms of Anxiety and Depression by Increasing Serotonin Levels: A Double-Blind, Randomized, Placebo-Controlled Study.

Background: Withania somnifera (Linn) or Ashwagandha is used in Ayurveda and other traditional medicine systems as an adaptogen and a neuroprotective supplement. Objective: The effect of Ashwagandha root extract (ARE) standardized for 2.5% full-spectrum withanolides as per The United States Pharmacopeia (USP) protocol with piperine (500 mg with 5 mg of 95% piperine) once a day (12.5 mg withanolides/day) was evaluated in individuals with mild to moderate depression and anxiety. Methods: In a randomized, double-blind placebo-controlled study, for 90 days, 70 participants were randomized to ARE (n = 34) or placebo (n = 36) once daily at night. Mean change in the Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS), Groningen Sleep Quality Scale (GSQS), and quality of life (QOL) from screening to days 30, 60, and 90 were evaluated. Safety was evaluated by monitoring any incidence of adverse events and laboratory parameters. Two-way analysis of variance (ANOVA) and repeated-measure ANOVA were used to compare ARE and placebo, and the changes within the group at different time points. Results: Seventy individuals were randomized and all of them completed the study. The HARS, HDRS, GSQS, and QOL scores improved significantly (p < 0.001) in all the participants taking ARE compared to placebo on days 30, 60, and 90. Anxiety and depression improved from baseline to end of the study in both groups, but the quantum of improvement was significantly higher in ARE. Serum levels of serotonin increased in ARE, but showed a decrease in placebo, the difference being statically significant (p < 0.001). Biochemical and hematological parameters remained in the normal range in all participants and ARE was well tolerated during the study. Conclusion: The results of the study suggest that 500 mg of ARE standardized for 2.5% withanolides with 5 mg piperine is beneficial in improving depression, and anxiety, by increasing serum serotonin levels. The trial was registered prospectively with the Clinical Trial Registry of India (CTRI) with the registration number CTRI/2022/05/042640, on May 18, 2022.

An Overview of the Pharmacological Properties of Calebin-A.

The natural polyphenol, calebin-A, was recently discovered and identified as a novel phytopharmaceutical with anti-inflammatory, anti-tumor, and antiproliferative properties. Calebin-A occurs naturally in trace quantities in Curcuma longa/C cassia, commonly known as turmeric, from the Zingiberaceae family. Calebin-A is a curcumin analog or 'chemical cousin' of curcumin with a similar chemical structure. Although few research studies have been conducted on the pharmacological and therapeutic properties of calebin-A, it is a very promising molecule with a variety of pharmacological properties. Some studies have suggested that calebin-A is helpful in treating various cancers due to its inhibitory effect on cell growth and anti-inflammatory properties. Other studies have suggested that calebin-A may improve neurocognitive status associated with neurodegeneration caused by Alzheimer's disease (AD) by inhibiting the aggregation of ß-amyloid. Finally, several studies have proposed that calebin-A may potentially be therapeutically beneficial in treating patients with obesity. This novel compound downregulates nuclear factor (NF)-κB-mediated processes involved with cancer, such as tumor cell invasion, proliferation, metastasis, and, most profoundly, inflammation. Moreover, calebin-A influences the activities of mitogen-activated protein kinases (MAPKs) in cancer cells. The present review identifies and discusses the pharmacological and phytochemical properties of calebin-A, as well as its therapeutic benefits and limitations, for future scientists and clinicians interested in exploring calebin-A's medicinal qualities.

A standardized Ashwagandha root extract alleviates stress, anxiety, and improves quality of life in healthy adults by modulating stress hormones: Results from a randomized, double-blind, placebo-controlled study.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has resulted in a surge in stress, anxiety, and depression worldwide. Ashwagandha, an ayurvedic adaptogen has been traditionally used to manage stress, anxiety, and general well-being. OBJECTIVE: We assessed the effect of Ashwagandha root extract (ARE-500 mg) standardized for 2.5% withanolides as per USP protocol with piperine (5 mg of 95% piperine) once daily for 60 days (12.5 mg withanolides/day) to alleviate stress and anxiety in healthy individuals with mild to moderate symptoms. METHODS: A randomized, double-blind, placebo-controlled study was conducted for 60 days using ARE (n = 27) and placebo (n = 27) once daily at night at Narayana Institute of Cardiac Sciences, Bangalore, and Vijaya Super Specialty Hospital, Nellore, in India. The objectives of this study were to assess an improvement in perceived stress scale (PSS), generalized anxiety disorder (GAD-7), quality of life (QOL), cognitive scores in the Cambridge Neuropsychological Test Automated Battery (CANTAB), changes in salivary cortisol, urinary serotonin, dopamine, serum levels of nitric oxide (NO), glutathione (GSH) and malondialdehyde (MDA) from baseline to end of the study. Safety was evaluated by laboratory parameters, and by monitoring any incidence of adverse events. RESULTS: 54 individuals were randomized and 50 of them completed the study. The PSS, GAD-7, and QOL scores improved significantly in all the participants taking ARE compared to the placebo. The CANTAB analysis revealed a significant improvement in multitasking, concentration, and decision taking time in ARE compared to placebo. ARE was also associated with a greater reduction in the morning salivary cortisol and an increase in urinary serotonin compared to placebo. Serum levels of NO, GSH, and MDA were not significantly different. Biochemical and hematological parameters remained in the normal range in all participants and ARE was well tolerated during the study. CONCLUSION: The results of the study suggest that ARE with 2.5% withanolides can effectively improve stress and anxiety by reducing cortisol and increasing serotonin in healthy individuals with mild to moderate symptoms.

A Short-Term Safety Evaluation of Silbinol®- an Extract from Pterocarpus marsupium in Healthy Adults- a Randomized, Double-Blind, Placebo-Controlled Study.

Background: Pterostilbene is an active molecule from the bark of the Pterocarpus marsupium tree with antioxidant and anti-inflammatory properties. Objective: This study aimed to evaluate the clinical safety of a standardized P. marsupium extract (PME) containing 90% pterostilbene (200 mg per day) in healthy adults. Methods: In a randomized, double-blind, placebo-controlled study, 60 healthy adult participants (27 males and 33 females) were randomized to receive PME-100 mg or placebo capsule twice a day for two months. The primary objectives of the study were to assess any changes in laboratory parameters, vital signs, and the occurrence of adverse events from screening to the final visit. Serum antioxidant enzyme levels were evaluated as a secondary outcome. Results: The hematological, lipid, glycemic, thyroid profiles and liver and renal functions remained within the normal range in all participants, with no difference between PME and placebo. Vital signs, including blood pressure, pulse rate, body weight, body mass index and electrocardiogram, did not reveal any significant differences between the PME and placebo groups at the beginning and end of the study. No serious adverse events were observed in any participant throughout the study period. The serum antioxidant profile was not significantly different between the treatment groups, although the glutathione levels were relatively higher in the PME group. Conclusions: Scientific evaluation of clinical safety of standardized extract is mandatory for its use as a supplement for various health benefits. The results of this study convincingly establish the safety of PME (>90% Pterostilbene) at 200 mg/day (100 mg bid) for human use. The study was approved by the Institutional Ethics Committee of BGS Global Institute of Medical Sciences & Hospital, Bangalore with the registration number CTRI/2019/08/020736.

Pharmacological activities of turmerones.

Turmerones are major bioactive compounds of Curcuma species with several beneficial pharmacological activities. In addition, various in vivo and in vitro studies noted that turmerones could affect different cytokines, metabolic pathways, and targets. Turmerones will have the potential to be a candidate agent to lessen many pathological and immunological conditions as a result of these pharmacological activities. In this review, we provided information about the pharmacological actions of turmerones using search engines such as PubMed, Google Scholar, Scopus, and Web of Science.

Probiotic modulation of gut microbiota by Bacillus coagulans MTCC 5856 in healthy subjects: A randomized, double-blind, placebo-control study.

BACKGROUND: Probiotics are known to rebalance the gut microbiota in dysbiotic individuals, but their impact on the gut microbiome of healthy individuals is seldom studied. The current study is designed to assess the impact and safety of Bacillus coagulans (Weizmannia coagulans) microbial type culture collection 5856 (LactoSpore®) supplementation on microbiota composition in healthy Indian adults. METHODS: The study participants (N = 30) received either LactoSpore (2 billion colony-forming units/capsule) or placebo for 28 days. The general and digestive health were assessed through questionnaires and safety by monitoring adverse events. Taxonomic profiling of the fecal samples was carried out by 16S rRNA amplicon sequencing using the Illumina MiSeq platform. The bacterial persistence was enumerated by quantitative reverse transcription-polymerase chain reaction. RESULTS: Gut health, general health, and blood biochemical parameters remained normal in all the participants. No adverse events were reported during the study. Metataxonomic analysis revealed minimal changes to the gut microbiome of otherwise healthy subjects and balance of Bacteroidetes and Firmicutes was maintained by LactoSpore. The relative abundance of beneficial bacteria like Prevotella, Faecalibacterium, Blautia, Megasphaera, and Ruminococcus showed an increase in probiotic-supplemented individuals. The quantitative polymerase chain reaction analysis revealed highly variable numbers of B. coagulans in feces before and after the study. CONCLUSION: The present study results suggest that LactoSpore is safe for consumption and does not alter the gut microbiome of healthy individuals. Minor changes in a few bacterial species may have a beneficial outcome in healthy individuals. The results reiterate the safety of B. coagulans microbial type culture collection 5856 as a dietary supplement and provide a rationale to explore its effect on gut microbiome composition in individuals with dysbiosis.

The effect of curcumin-piperine on cardiometabolic, inflammatory and oxidative stress factors and macular vascular density in optical coherence tomography angiography (OCTA) in patients with non-proliferative diabetic retinopathy: Study protocol for a randomized, double-blind controlled trial.

Objective: Curcumin is a safe phytochemical with antioxidant, anti-inflammatory, antidiabetic, and lipid-lowering effects. This study aims to investigate the efficacy of curcumin-piperine in non-proliferative diabetic retinopathy. Materials and Methods: In this double-blind randomized trial, 60 diabetic retinopathy patients after meeting the inclusion criteria will be randomly assigned to two groups of curcumin-piperine supplementation (1000 mg per day for 12 weeks) or receiving placebo. The density of small blood vessels in the retina by optical coherence tomography angiography (OCTA), fasting blood glucose, triglyceride, renal indices (blood urea nitrogen and creatinine), high-sensitivity C-reactive protein, total antioxidant capacity, total oxidant status, body mass index, waist circumference, and weight will be measured. Conclusion: If the beneficial effects of curcumin on diabetic retinopathy are observed, this safe, this natural and inexpensive herbal supplement can be considered a therapeutic solution in these patients.

Antiviral Mechanisms of Curcumin and Its Derivatives in Prevention and Treatment of COVID-19: A Review.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now plagued the world for almost 3 years. Although vaccines are now available, the severity of the pandemic and the current dearth of approved effective medications have prompted the need for novel treatment approaches. Curcumin, as a food nutraceutical with anti-inflammatory and antioxidant effects, is now under consideration for the prevention and treatment of COVID-19. Curcumin has been demonstrated to retard the entrance of SARS-CoV-2 into cells, interfere with its proliferation inside cells, and curb the hyperinflammatory state caused by the virus by modulating immune system regulators, minimizing the cytokine storm effect, and modulating the renin-angiotensin system. This chapter discusses the role of curcumin and its derivatives in the prevention and treatment of COVID-19 infection, considering the molecular mechanisms involved. It will also focus on the molecular and cellular profiling techniques as essential tools in this research, as these can be used in the identification and development of new biomarkers, drug targets, and therapeutic approaches for improved patient care.

Evaluation of Curcumin-Piperine Supplementation in COVID-19 Patients Admitted to the Intensive Care: A Double-Blind, Randomized Controlled Trial.

BACKGROUND: Curcumin is a traditional remedy for diseases associated with hyper-inflammatory responses and immune system impairment. Piperine, a bioactive compound in black pepper, has the potential to enhance curcumin bioavailability. 0This study aims to examine the effect of the curcumin-piperine co-supplementation in patients infected with SARS-CoV-2 and admitted to the intensive care unit (ICU). MATERIAL AND METHODS: In this parallel randomized, double-blind, placebo-controlled trial, 40 patients with COVID-19 admitted to ICU were randomized to receive three capsules of curcumin (500 mg)-piperine (5 mg) or placebo for 7 days. RESULTS: After 1 week of the intervention, serum aspartate aminotransferase (AST) (p = 0.02) and C-reactive protein (CRP) (p = 0.03) were significantly decreased, and hemoglobin was increased (p = 0.03) in the curcumin-piperine compared to the placebo group. However, compared with the placebo, curcumin-piperine had no significant effects on the other biochemical, hematological, and arterial blood gas and 28-day mortality rate was three patients in each group (p = 0.99). CONCLUSION: The study results showed that short-term curcumin-piperine supplementation significantly decreased CRP, AST, and increased hemoglobin in COVID-19 patients admitted to the ICU. Based on these promising findings, curcumin appears to be a complementary treatment option for COVID-19 patients, although some parameters were not affected by the intervention.

The impact of curcumin on migraine: A comprehensive review.

Migraine, a neurovascular condition, is a chronic and lifelong disease that affects about 15% of the population worldwide. Although the exact pathophysiology and etiology of migraine are still unclear, oxidative stress, inflammation, and neuroendocrine imbalances are identified as the critical risk factors for migraine attacks. Curcumin is an active component and a polyphenolic diketone compound extracted from turmeric. Curcumin is a promising candidate for preventing and controlling migraine due to its anti­inflammatory, antioxidative, anti-protein aggregate, and analgesic effects. In the present review, we have evaluated experimental and clinical studies investigating the impact of liposomal curcumin and nano-curcumin on the frequency and severity of migraine attacks in patients. Although the results are promising, more studies should be conducted in this area to show the exact efficacies of curcumin on clinical symptoms of migraine and investigate its potential mechanisms.

A Randomized Double-Blind, Placebo-Controlled Study to Evaluate the Anti-Skin-Aging Effect of LactoSporin - The Extracellular Metabolite from Bacillus coagulans (Weizmannia coagulans) MTCC 5856 in Healthy Female Volunteers.

Purpose: There has been a growing interest in the use of probiotics and their products for skin care, over the last decade. LactoSporin is the extracellular metabolite of a spore-forming probiotic Bacillus coagulans (Weizmannia coagulans) MTCC 5856, with antimicrobial and skin protecting activity. Patients and Methods: The anti-skin-aging potential of LactoSporin was evaluated in a randomized, double-blinded, placebo-controlled study in healthy female participants (70 screened and 56 randomized). The participants applied either LactoSporin or matched placebo formulation (N=28 in each group) for 10 weeks, and the effects were assessed by dermatological, and non-invasive instrument-based evaluation using Antera, Cutometer, Corneometer, and Tewameter. All the 56 participants completed the study and were included for the analysis. Results: The regular use of LactoSporin cream for 10 weeks showed a significant reduction in visibility of wrinkles around crow's feet, nasolabial folds, frown lines, and facial fine lines compared to baseline and placebo by dermatological and Antera assessments. LactoSporin showed improvement in skin elasticity and hydration by dermatological assessments, but the effect was not significantly different from placebo when assessed by Cutometer, Corneometer, and Tewameter. No adverse events or skin irritation was observed in any participants during the study. Conclusion: These results suggest that LactoSporin could be a safe natural ingredient to reduce wrinkles and fine lines in cosmetic formulations.

A minor metabolite from Curcuma longa effective against metabolic syndrome: results from a randomized, double-blind, placebo-controlled clinical study.

Metabolic syndrome (MetS) is characterized by the presence of at least three interrelated risk factors, including central obesity, hypertension, elevated serum triglycerides, low serum high-density lipoproteins, and insulin resistance. Abdominal obesity is considered a predominant risk factor. Lifestyle changes with medications to lower cholesterol, blood sugar, and hypertension are the general treatment approaches. Functional foods and bioactive food ingredients represent versatile tools for addressing different aspects of MetS. In a randomized placebo-controlled clinical study, we evaluated the effect of Calebin A, a minor bioactive phytochemical from Curcuma longa, on metabolic syndrome in obese adults (N = 100), and 94 individuals completed the study (N = 47 in both groups). They were subjected to Calebin A supplementation for 90 days, which resulted in a statistically significant reduction in their body weight, waist circumference, body mass index, low-density lipoprotein-cholesterol, and triglyceride levels compared to those with the placebo. A small but significant increase in high-density lipoprotein-cholesterol levels was also observed in these individuals. Furthermore, Calebin A showed a positive effect on adipokines by reducing circulating leptin levels. Finally, C-reactive protein levels were significantly reduced in Calebin A-supplemented individuals, suggesting a beneficial impact on managing MetS-induced inflammation. Blood glucose levels, insulin resistance, and blood pressure levels were not affected by Calebin A. In conclusion, Calebin A may be an effective supplement for managing abdominal obesity, dyslipidemia, and systemic inflammation in individuals with metabolic syndrome. This study was prospectively registered on the Clinical Trial Registry of India (CTRI) with the registration number CTRI/2021/09/036495. https://ctri.nic.in/Clinicaltrials/advancesearchmain.php.

The Combined Effect of Curcumin and Crocin on the Reduction of Inflammatory Responses in Arthritic Rats.

The present study evaluated the anti-arthritic impact of combined crocin and curcumin on Adjuvant Induced Arthritis (AIA) in rats. Arthritis model was induced in rats by injecting Complete Freund's adjuvant (CFA) into the right hind paw and was subsequently treated with crocin and curcumin. Evaluation of anti-arthritic activity was carried out using paw swelling, hematological parameters, biochemical parameters, inflammatory cytokines, and histopathology of rats. The results showed increased paw swelling, increased serum markers levels, including CRP, RF, ALP, ALT, and AST, and inflammatory cytokines (ILlß and TNFα) along with histology changes (cartilage and bone degradation) in arthritic rats when compared to the normal group. Crocin, curcumin and crocin + curcumin administration at different doses (especially combination at 40 mg/kg and 30 mg/kg respectively), as well as MTX revealed suitable therapeutic effect on AIA rats. Moreover, both phytochemicals and their combination at different doses showed effective anti-arthritic effects owing to their anti-inflammatory effects. Therefore, crocin and curcumin, either alone or in combination, can be a suitable treatment modality for rheumatoid arthritis .

The effects of Bacillus coagulans MTCC 5856 on functional gas and bloating in adults: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Gut microbiome dysbiosis is a major cause of abdominal gas, bloating, and distension. Bacillus coagulans MTCC 5856 (LactoSpore) is a spore-forming, thermostable, lactic acid-producing probiotic that has numerous health benefits. We evaluated the effect of Lacto Spore on improving the clinical symptoms of functional gas and bloating in healthy adults. METHODS: Multicenter, randomized, double-blind, placebo-controlled study at hospitals in southern India. Seventy adults with functional gas and bloating with a gastrointestinal symptom rating scale (GSRS) indigestion score ≥ 5 were randomized to receive B coagulans MTCC 5856 (2 billion spores/day, N = 35) or placebo (N = 35) for 4 weeks. Changes in the GSRS-Indigestion subscale score for gas and bloating and global evaluation of patient's scores from screening to the final visit were the primary outcomes. The secondary outcomes were Bristol stool analysis, brain fog questionnaire, changes in other GSRS subscales, and safety. RESULTS: Two participants from each group withdrew from the study and 66 participants (n = 33 in each group) completed the study. The GSRS indigestion scores changed significantly (P < .001) in the probiotic group (8.91-3.06; P < .001) compared to the placebo (9.42-8.43; P = .11). The median global evaluation of patient's scores was significantly better (P < .001) in the probiotic group (3.0-9.0) than in the placebo group (3.0-4.0) at the end of the study. The cumulative GSRS score, excluding the indigestion subscale, decreased from 27.82 to 4.42% (P < .001) in the probiotic group and 29.12 to 19.33% (P < .001) in the placebo group. The Bristol stool type improved to normal in both the groups. No adverse events or significant changes were observed in clinical parameters throughout the trial period. CONCLUSIONS: Bacillus coagulans MTCC 5856 may be a potential supplement to reduce gastrointestinal symptoms in adults with abdominal gas and distension.

Curcumin and chemokines: mechanism of action and therapeutic potential in inflammatory diseases.

Chemokines belong to the family of cytokines with chemoattractant properties that regulate chemotaxis and leukocyte migration, as well as the induction of angiogenesis and maintenance of hemostasis. Curcumin, the major component of the Curcuma longa rhizome, has various pharmacological actions, including anti-inflammatory, immune-regulatory, anti-oxidative, and lipid-modifying properties. Chemokines and chemokine receptors are influenced/modulated by curcumin. Thus, the current review focuses on the molecular mechanisms associated with curcumin's effects on chemoattractant cytokines, as well as putting into context the many studies that have reported curcumin-mediated regulatory effects on inflammatory conditions in the organs/systems of the body (e.g., the central nervous system, liver, and cardiovascular system). Curcumin's effects on viral and bacterial infections, cancer, and adverse pregnancy outcomes are also reviewed.