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Superoxide anion radical induced phototoxicity of 2,4,5,6-Tetraminopyrimidine sulfate via mitochondrial-mediated apoptosis in human skin keratinocytes at ambient UVR exposure.
Shukla, S, Chopra, D, Patel, SK, Negi, S, Srivastav, AK, Ch, R, Bala, L, Dwivedi, A, Ray, RS
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2022;:112990
Abstract
2,4,5,6-Tetraaminopyrimidine sulfate (TAPS) is worldwide the most commonly used developer in hair dyes. As skin is the major organ, which is directly exposed to these permanent hair dyes, a comprehensive dermal safety assessment is needed. Hereto, we studied the photosensitization potential and mechanism involved in dermal phototoxicity of TAPS exposed to the dark and UVA/UVB/Sunlight by using different in-chemico and mammalian (HaCaT) cells, as test systems. Our experimental outcomes illustrate that TAPS get photodegraded (LC-MS/MS) and specifically generated superoxide anion radical (O2•-) under UVA and UVB via type-I photodynamic reaction. The phototoxic potential of TAPS is measured through MTT, NRU, and LDH assays that depicted a significant cell viability reduction at 25 μg/ml concentration and higher. Different cellular stainings (PI uptake, AO/EB, JC-1, NR uptake) suggested the role of mitochondrial-mediated apoptosis. Further, the transcriptomics study revealed upregulation of Apaf-1, Bax, Cytochrome c, Caspase 3, Caspase 9 and downregulation of Catalase and Bcl-2 by TAPS treated cells that strengthen our findings. Thus, the above findings suggest that chronic application of TAPS may be hazardous for human skin and promote various skin diseases.
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Adverse Drug Reactions to Radiographic Contrast Media in a Teaching Hospital in North India: An Observational Study.
Chopra, D, Jain, A, Garg, R, Dhingra, S
Current drug safety. 2019;(2):122-126
Abstract
BACKGROUND Radiocontrast media are used extensively nowadays to visualize internal organs. Currently, non-ionic iodinated contrast media are used which are generally considered to be safe but some adverse reactions have been reported. Thus, the present study was carried out to analyze the nature and incidence of adverse drug reactions (ADRs) to radiographic contrast media in a teaching hospital. METHODS An observational study carried out for a period of six months in a teaching hospital. Contrast media induced adverse reactions were analyzed in terms of affected organs, rate, causality assessment, severity and preventability. The treatment and outcomes of adverse events were also recorded. Naranjo Probability Scale was used to evaluate the relationship between the contrast agent used and the suspected ADR. The severity of the suspected ADRs was determined using Hartwig Scale and preventability was assessed using modified Schumock and Thornton criterion. RESULTS A total of 15 suspected ADRs occurred in 11 patients with an incidence of 1.4%. It included 5 (45.4%) males and 6 (54.5%) females (p < 05). The highest percentage (72.7 %) of ADRs was seen in adult patients, the mean age being 40.8 years. Vomiting (33.3%) was the most common ADR noted followed by severe nausea and rashes. 64.7 % of ADRs were categorized as probable and 35.3 % were possible. Adverse reactions required treatment in 46.6% patients. There was no fatality reported. CONCLUSION The reactions observed were mild to moderate in severity and occurred within 30 minutes of the administration of the contrast.
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Prebiotic Potential of Herbal Medicines Used in Digestive Health and Disease.
Peterson, CT, Sharma, V, Uchitel, S, Denniston, K, Chopra, D, Mills, PJ, Peterson, SN
Journal of alternative and complementary medicine (New York, N.Y.). 2018;24(7):656-665
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Triphala, licorice and slippery elm are key treatments for gastrointestinal health and disease in traditional systems of medicine. Prebiotics are defined as undigested dietary carbohydrates that alter the gut microbiota and promote human health. They reach the site of action in the colon mostly unmetabolized and are broken down by enzymes. The aim of the study was to find out whether the complex carbohydrates present in herbal medicine may be strong drivers to modulate gut microbiota composition. The study recruited 12 healthy men and women, aged between 30-60 years who had previously followed a vegan or vegetarian diet for more than 1 year, to donate a single stool sample. Results show that both the sugar and protein content of these herbal medicines drive alterations in gut microbiota profiles. Each of these herbal medicines studied, uniquely altered gut bacteria communities. Authors conclude that the health benefits of these herbs are mostly due to their ability to alter the gut microbiota in a manner that is predicted to improve colonic epithelium function, reduce inflammation, and promote protection from bacterial pathogenic infection.
Abstract
INTRODUCTION The prebiotic potential of herbal medicines has been scarcely studied. METHODS The authors therefore used anaerobic human fecal cultivation to investigate whether three herbal medicines commonly used in gastrointestinal health and disease in Ayurveda alter the growth and abundance of specific bacterial species. RESULTS Profiling of cultures supplemented with Glycyrrhiza glabra, Ulmus rubra, or triphala formulation by 16S rDNA sequencing revealed profound changes in diverse taxa in human gut microbiota. Principal coordinate analysis highlights that each herbal medicine drives the formation of unique microbial communities. The relative abundance of approximately one-third of the 299 species profiled was altered by all 3 medicines, whereas additional species displayed herb-specific alterations. Herb supplementation increased the abundance of many bacteria known to promote human health, including Bifidobacterium spp., Lactobacillus spp., and Bacteroides spp. Herb supplementation resulted in the reduced relative abundance of many species, including potential pathogens such as Citrobacter freundii and Klebsiella pneumoniae. Herbal medicines induced blooms of butyrate- and propionate-producing species. U. rubra and triphala significantly increased the relative abundance of butyrate-producing bacteria, whereas G. glabra induced the largest increase in propionate-producing species. To achieve greater insight into the mechanisms through which herbal medicines alter microbial communities, the authors assessed the shifts in abundance of glycosyl hydrolase families induced by each herbal medicine. Herb supplementation, particularly G. glabra, significantly increased the representation and potential expression of several glycosyl hydrolase families. DISCUSSION These studies are novel in highlighting the significant prebiotic potential of medicinal herbs and suggest that the health benefits of these herbs are due, at least in part, to their ability to modulate the gut microbiota in a manner predicted to improve colonic epithelium function, reduce inflammation, and protect from opportunistic infection. Forthcoming studies in human clinical trials will test the concordance of the results generated in vitro and the predictions made by genome analyses.
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Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.
Peterson, CT, Vaughn, AR, Sharma, V, Chopra, D, Mills, PJ, Peterson, SN, Sivamani, RK
Journal of evidence-based integrative medicine. 2018;:2515690X18790725
Abstract
BACKGROUND Curcuma longa (common name: turmeric) and one of its biologically active constituents, curcumin, have received increased clinical attention. Insufficient data exist on the effects of curcumin and turmeric on the gut microbiota and such studies in humans are lacking. METHODS Turmeric tablets with extract of piperine (Bioperine) (n = 6), curcumin with Bioperine tablets (n = 5), or placebo tablets (n = 3) were provided to healthy human subjects and subsequent changes in the gut microbiota were determined by 16S rDNA sequencing. RESULTS The number of taxa detected ranged from 172 to 325 bacterial species. The placebo group displayed an overall reduction in species by 15%, whereas turmeric-treated subjects displayed a modest 7% increase in observed species posttreatment. Subjects taking curcumin displayed an average increase of 69% in detected species. The gut microbiota response to treatment was highly personalized, thus leading to responders and nonresponders displaying response concordance. These "responsive" subjects defined a signature involving uniform increases in most Clostridium spp., Bacteroides spp., Citrobacter spp., Cronobacter spp., Enterobacter spp., Enterococcus spp., Klebsiella spp., Parabacteroides spp., and Pseudomonas spp. Common to these subjects was the reduced relative abundance of several Blautia spp. and most Ruminococcus spp. CONCLUSIONS All participants' microbiota displayed significant variation over time and individualized response to treatment. Among the responsive participants, both turmeric and curcumin altered the gut microbiota in a highly similar manner, suggesting that curcumin may drive the majority of observed changes observed in turmeric-treated subjects.
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Therapeutic Uses of Triphala in Ayurvedic Medicine.
Peterson, CT, Denniston, K, Chopra, D
Journal of alternative and complementary medicine (New York, N.Y.). 2017;(8):607-614
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Abstract
AIM: The aim of this article is to review the current literature on the therapeutic uses and efficacy of Triphala. Herbal remedies are among the most ancient medicines used in traditional systems of healthcare such as Ayurveda. Triphala, a well-recognized and highly efficacious polyherbal Ayurvedic medicine consisting of fruits of the plant species Emblica officinalis (Amalaki), Terminalia bellerica (Bibhitaki), and Terminalia chebula (Haritaki), is a cornerstone of gastrointestinal and rejuvenative treatment. METHODS A search of the PubMed database was conducted. RESULTS In addition, numerous additional therapeutic uses described both in the Ayurvedic medical literature and anecdotally are being validated scientifically. In addition to laxative action, Triphala research has found the formula to be potentially effective for several clinical uses such as appetite stimulation, reduction of hyperacidity, antioxidant, anti-inflammatory, immunomodulating, antibacterial, antimutagenic, adaptogenic, hypoglycemic, antineoplastic, chemoprotective, and radioprotective effects, and prevention of dental caries. Polyphenols in Triphala modulate the human gut microbiome and thereby promote the growth of beneficial Bifidobacteria and Lactobacillus while inhibiting the growth of undesirable gut microbes. The bioactivity of Triphala is elicited by gut microbiota to generate a variety of anti-inflammatory compounds. CONCLUSIONS This review summarizes recent data on pharmacological properties and clinical effects of Triphala while highlighting areas in need of additional investigation and clinical development.
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Identification of Altered Metabolomic Profiles Following a Panchakarma-based Ayurvedic Intervention in Healthy Subjects: The Self-Directed Biological Transformation Initiative (SBTI).
Peterson, CT, Lucas, J, John-Williams, LS, Thompson, JW, Moseley, MA, Patel, S, Peterson, SN, Porter, V, Schadt, EE, Mills, PJ, et al
Scientific reports. 2016;:32609
Abstract
The effects of integrative medicine practices such as meditation and Ayurveda on human physiology are not fully understood. The aim of this study was to identify altered metabolomic profiles following an Ayurveda-based intervention. In the experimental group, 65 healthy male and female subjects participated in a 6-day Panchakarma-based Ayurvedic intervention which included herbs, vegetarian diet, meditation, yoga, and massage. A set of 12 plasma phosphatidylcholines decreased (adjusted p < 0.01) post-intervention in the experimental (n = 65) compared to control group (n = 54) after Bonferroni correction for multiple testing; within these compounds, the phosphatidylcholine with the greatest decrease in abundance was PC ae C36:4 (delta = -0.34). Application of a 10% FDR revealed an additional 57 metabolites that were differentially abundant between groups. Pathway analysis suggests that the intervention results in changes in metabolites across many pathways such as phospholipid biosynthesis, choline metabolism, and lipoprotein metabolism. The observed plasma metabolomic alterations may reflect a Panchakarma-induced modulation of metabotypes. Panchakarma promoted statistically significant changes in plasma levels of phosphatidylcholines, sphingomyelins and others in just 6 days. Forthcoming studies that integrate metabolomics with genomic, microbiome and physiological parameters may facilitate a broader systems-level understanding and mechanistic insights into these integrative practices that are employed to promote health and well-being.
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The Self-Directed Biological Transformation Initiative and Well-Being.
Mills, PJ, Wilson, KL, Pung, MA, Weiss, L, Patel, S, Doraiswamy, PM, Peterson, CT, Porter, V, Schadt, E, Chopra, D, et al
Journal of alternative and complementary medicine (New York, N.Y.). 2016;(8):627-34
Abstract
OBJECTIVE To examine the effects of a comprehensive residential mind-body program on well-being. DESIGN The Self-Directed Biological Transformation Initiative was a quasi-randomized trial comparing the effects of participation in a 6-day Ayurvedic system of medicine-based comprehensive residential program with a 6-day residential vacation at the same retreat location. SETTING Retreat setting. PARTICIPANTS 69 healthy women (n = 58) and men (n = 11) (mean age ± standard deviation, 53.6 ± 12 years). INTERVENTION The Ayurvedic intervention addressed physical and emotional well-being through group meditation and yoga, massage, diet, adaptogenic herbs, lectures, and journaling. OUTCOME MEASURES A battery of standardized questionnaires. RESULTS Participants in the Ayurvedic program showed significant and sustained increases in ratings of spirituality (p < 0.01) and gratitude (p < 0.05) compared with the vacation group, which showed no change. The Ayurvedic participants also showed increased ratings for self-compassion (p < 0.01) as well as less anxiety at the 1-month follow-up (p < 0.05). CONCLUSIONS Findings suggest that a short-term intensive program providing holistic instruction and experience in mind-body healing practices can lead to significant and sustained increases in perceived well-being and that relaxation alone is not enough to improve certain aspects of well-being.
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Revisiting Terminalia arjuna - An Ancient Cardiovascular Drug.
Dwivedi, S, Chopra, D
Journal of traditional and complementary medicine. 2014;(4):224-31
Abstract
Terminalia arjuna, commonly known as arjuna, belongs to the family of Combretaceae. Its bark decoction is being used in the Indian subcontinent for anginal pain, hypertension, congestive heart failure, and dyslipidemia, based on the observations of ancient physicians for centuries. The utility of arjuna in various cardiovascular diseases needs to be studied further. Therefore, the present review is an effort to give a detailed survey of the literature summarizing the experimental and clinical studies pertinent to arjuna in cardiovascular disorders, which were particularly performed during the last decade. Systematic reviews, meta-analyses, and clinical studies of arjuna were retrieved through the use of PubMed, Google Scholar, and Cochrane databases. Most of the studies, both experimental and clinical, have suggested that the crude drug possesses anti-ischemic, antioxidant, hypolipidemic, and antiatherogenic activities. Its useful phytoconstituents are: Triterpenoids, β-sitosterol, flavonoids, and glycosides. Triterpenoids and flavonoids are considered to be responsible for its beneficial antioxidant cardiovascular properties. The drug has shown promising effect on ischemic cardiomyopathy. So far, no serious side effects have been reported with arjuna therapy. However, its long-term safety still remains to be elucidated. Though it has been found quite useful in angina pectoris, mild hypertension, and dyslipidemia, its exact role in primary/secondary coronary prevention is yet to be explored.
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Evaluation of efficacy and safety of fixed dose combination of glimepiride 2 mg pluspioglitazone 15 mg plus metformin SR 500 mg in the management of patients with type-2 diabetes mellitus.
Meshram, DM, Langade, DG, Kinagi, SB, Naikwadi, AA, Morye, V, Chopra, D
Journal of the Indian Medical Association. 2005;(8):447-50
Abstract
An estimated 25 million Indians currently have diabetes and the projections indicate Indians would be the largest group by the year 2025 AD. An open, phase III, multicentric study was conducted to determine the efficacy and tolerability of the triple drug combination glimepiride 2 mg plus pioglitazone hydrochloride 15 mg plus metformin SR 500 mg for 8 weeks in 101 Indian patients with type 2 diabetes mellitus. The study revealed that the triple drug combination could achieve the recommended goals, recommended by American Diabetic Association, for fasting blood glucose < or = 140 mg/dl and glycosylated haemoglobin (HbA1c) of < or = 8%. After 8 weeks, the mean fasting blood glucose (baseline 189.61) was reduced to 111.68 (41% reduction); the mean glycosylated haemoglobin (baseline 10.32) was significantly reduced to 7.54 (26% reduction). The triple drug combination significantly reduced the levels of triglyceride, low density lipoproteins and total cholesterol. These significant levels were achieved within 8 weeks and all patients tolerated the drug well with no reported case of serious adverse events including hypoglycaemia. There were also no reported drug interactions in the study. Since the decrease in HbA1c was continuous and throughout the study, a further decrease in the HbA1c levels would have been noted since the present trial was designed for a period of 8 weeks. Thus, the present study confirms the efficacy and safety of FDC of the triple drug combination in patients with type 2 diabetes.