Garcinia indica extract standardized for 20% Garcinol reduces adipogenesis and high fat diet-induced obesity in mice by alleviating endoplasmic reticulum stress

Majeed, Muhammed; Majeed, Shaheen; Nagabhushanam, Kalyanam; Lawrence, Lincy; Mundkur, Lakshmi

doi:10.1016/j.jff.2020.103863

Cited by 12 publications

(11 citation statements)

References 41 publications

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“…Curcuminoids have been subjected to several preclinical and clinical studies for its health benefits related to chronic inflammatory diseases, and Garcinol has been evaluated for its anti-cancer activities and anti-obesity activity by preventing gut dysbiosis which is one of the contributing factors for NAFLD 81 . GIE has been reported to have anti adipogenesis activity and we have also reported an anti-obesity activity of GIE by reducing ER stress and activating adipocyte browning 82 . GIE is thus likely to have a positive effect on reducing steatosis, while curcuminoids being potent anti-inflammatory molecules act on inflammatory pathways.…”

Section: Discussionsupporting

confidence: 59%

Novel Combinatorial Regimen of Garcinol and Curcuminoids for Non-alcoholic Steatohepatitis (NASH) in Mice

Majeed

Nagabhushanam

et al. 2020

Sci Rep

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Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver disease (NAFLD), a chronic liver disease with a significant unmet clinical need. In this study, we examined the protective effects of Garcinia indica extract standardized to contain 20% w/w of Garcinol (GIE) and 95% Curcuminoids w/w from Curcuma longa (Curcuminoids) in a Stelic animal model (STAM) of NASH. The STAM mice developed steatosis, hepatocyte ballooning, and inflammation, which were significantly reduced by the combination of GIE and Curcuminoids, resulting in a lower NAFLD activity score. The treatment reduced fibrosis as observed by Sirius red staining, liver hydroxyproline content and mRnA levels of tGf-β and collagen in the liver. Immunostaining with alpha-smooth muscle actin (α SMA) revealed a significant reduction in hepatic stellate cells. Intriguingly, the combination regimen markedly decreased the mRNA levels of MCP1 and CRP and both mRNA and protein levels of TNF-α. NF-kB, reduced the hepatic and circulating FGF21 levels and altered the nonenzymatic (glutathione) and enzymatic antioxidant markers (Glutathione peroxidase, and superoxide dismutase). Our results suggest that the combination of GIE and Curcuminoids can reduce the severity of NASH by reducing steatosis, fibrosis, oxidative stress, and inflammation. The results suggest that the combinatorial regimen could be an effective supplement to prevent the progression of liver steatosis to inflammation and fibrosis in NASH. Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disorders 1,2. It includes the spectrum of liver disease, ranging from benign fatty liver to hepatocellular carcinoma. It is histologically further categorized into the nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL, as the early-stage disease shows the presence of excessive fat in the liver (hepatic steatosis) with no evidence of hepatocellular injury, while NASH is characterized by the accumulation of fat accompanied by infiltration of inflammatory cells and cellular damage, which can progress to cirrhosis, liver failure, and liver cancer 3. NASH is the hepatic manifestation of metabolic disorder and is closely associated with type 2 diabetes, obesity, insulin resistance anda systemic inflammatory state 4-8. Consequently, NASH patients have a higher risk of cardiovascular events and neoplasia, resulting in a higher rate of mortality 9,10. It is usually a silent disease with minimum symptoms, while weight loss, fatigue, and weakness develop as the disease progresses. Although the disease development and progression are still not well elucidated, the most accepted theory to explain the pathogenesis is "multiple-hits hypothesis". The initial hit leads to the development of simple steatosis, while liver cell inflammation and apoptosis are induced by secondary hits, leading to mitochondrial dysfunction, oxidative stress, lipid peroxidation, gut dysbiosis, and Kupffer cell activation, which finally results in NASH 11,12. Presence...

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Section: Discussionsupporting

confidence: 59%

Novel Combinatorial Regimen of Garcinol and Curcuminoids for Non-alcoholic Steatohepatitis (NASH) in Mice

Majeed

Nagabhushanam

et al. 2020

Sci Rep

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“…Garcinol was found to be structurally similar to curcumin (an anticancer agent), because of the presence of β-diketone and showed better anticancer activity compared to Membranes 2021, 11, 992 2 of 11 curcumin [7]. Garcinol reduces obesity by acting on the AMPK-ER stress axis [8] and was also reported to modulate gut microbiota and reduce obesity in mice [9]. To further support these preclinical studies and to accelerate the development of garcinol as a potential drug candidate, additional studies like in-vitro transport and metabolism are required [6].…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450 and P-gp Mediated Herb-Drug Interactions and Molecular Docking Studies of Garcinol

Bolla¹,

Srivastava²,

Ravichandiran

et al. 2021

Membranes

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Garcinol is an active constituent of Garcinia indica and Garcinia cambogia. Recent studies have proven that garcinol has anti-inflammatory, anti-cancer, and anti-oxidant activities. The objective of this study was to evaluate the inhibitory effects of garcinol on the activities of the drug metabolizing cytochrome P450 (CYP) isozymes to predict potential herb-drug interactions with co-administered drugs. Garcinol was incubated with a mixture of rat liver microsomes and eight CYP probe substrate cocktail under optimized incubation conditions and the samples were analyzed using a validated method on LC-MS/MS. Garcinol showed strong inhibition with IC50 values of CYP1A2 (7.6 µM), CYP2C9 (8.0 µM), CYP2B6 (2.1 µM), CYP2D6 (9.5 µM), and CYP3A4 (5.1 µM), respectively, and moderate inhibition towards CYP2C19 (16.4 µM) and CYP2E1 (19.0 µM). Molecular docking studies were performed on garcinol against the active sites of CYP2B6 and CYP3A4 proteins. These results further confirmed that the inhibitory activity of garcinol occurred by occupying the active sites of these human CYPs and by making favorable interactions with its key residues. In-vivo CYP inhibition studies were carried out in Sprague-Dawley rats. These results suggest garcinol may cause herb-drug interactions, mediated by inhibition of CYPs involved in drug metabolism in-vivo by altering the pharmacokinetic parameters like AUC and Cmax in a clinically significant manner. Garcinol was found to upregulate the expression and activity of P-gp in western blotting study and P-gp inhibition study in-vivo. These findings give a clear understanding to predict potential herb-drug/drug-drug interactions of garcinol for safe clinical use in future.

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“…The ethanolic extracts of Actaea racemosa L. have been proven as the best candidate for treatment of obesity and related diseases for further studies [205]. Garcinia indica extract standardized for 20% Garcinol inhibited adipogenesisin vitro3T3-L1 cells, decreased endoplasmic reticulum stress in adipocytes, alleviated visceral fat weight, and regulated obesity by acting on the AMPK-ER stress axis [206]. Chrysin is a flavonoid found in plant extracts from Passiflora species, alleviated the body weight of rats, decreased calorie intake of rats, and the hypertrophy of adipocytes [207].…”

Section: Solanaceaementioning

confidence: 99%

Natural Dietary and Medicinal Plants with Anti-Obesity Therapeutics Activities for Treatment and Prevention of Obesity during Lock Down and in Post-COVID-19 Era

2021

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Overweight and obesity have become global epidemics, especially during the lockdown due to the COVID-19 pandemic. The potential of medicinal plants as a better and safe option in treating obesity and overweight has gained attention in recent years. Obesity and overweight has become a major public health concern, and its incidence rising at an alarming rate. Obesity is one of the major types of metabolic syndrome, resulting in various types of problems such as hypertension, diabetes, dyslipidemia, and excess fat accumulation. The current searching was done by the keywords in main indexing systems including Scopus, PubMed/MEDLINE, the search engine of Google Scholar, and Institute for Scientific Web of Science. The keywords were traditional medicine, health benefits, pharmaceutical science, pomegranate, punicalin, punicalagin, and ellagitannins. Google Scholar was searched manually for possible missing manuscripts, and there was no language restriction in the search. This review was carried out to highlight the importance of medicinal plants which are common in traditional medicinal sciences of different countries, especially Asia to prevent and treatment of obesity and overweight during the global pandemic and the post-COVID-19 era.

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Garcinia indica extract standardized for 20% Garcinol reduces adipogenesis and high fat diet-induced obesity in mice by alleviating endoplasmic reticulum stress

Cited by 12 publications

References 41 publications

Novel Combinatorial Regimen of Garcinol and Curcuminoids for Non-alcoholic Steatohepatitis (NASH) in Mice

Novel Combinatorial Regimen of Garcinol and Curcuminoids for Non-alcoholic Steatohepatitis (NASH) in Mice

Cytochrome P450 and P-gp Mediated Herb-Drug Interactions and Molecular Docking Studies of Garcinol

Natural Dietary and Medicinal Plants with Anti-Obesity Therapeutics Activities for Treatment and Prevention of Obesity during Lock Down and in Post-COVID-19 Era

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