Multi-Mechanistic and Therapeutic Exploration of Nephroprotective Effect of Traditional Ayurvedic Polyherbal Formulation Using In Silico, In Vitro and In Vivo Approaches.

Based on traditional therapeutic claims, NEERI KFT (a traditional Ayurvedic polyherbal preparation) has been innovatively developed in recent time on the decades of experience for treating kidney dysfunction. Due to the lack of scientific evidence, the present investigations are needed to support the rationale use of NEERI KFT. Considering the facts, the study investigated the nephroprotective effect of NEERI KFT against kidney dysfunction using in silico, in vitro and in vivo approaches. In this study, phytochemical and network pharmacology studies were performed for the developed formulation to evaluate the molecular mechanism of NEERI KFT in the amelioration of kidney disease. In vitro nephroprotective and antioxidant effect of NEERI KFT was determined on HEK 293 cells against cisplatin-induced cytotoxicity and oxidative stress. In vivo nephroprotective effect of NEERI KFT was determined against cisplatin-induced nephrotoxicity in Wistar rats, via assessing biochemical markers, antioxidant enzymes and inflammatory cytokines such as TNF-α, IL-1ß, CASP-3, etc. The results showed that the compounds such as gallic acid, caffeic acid and ferulic acid are the major constituents of NEERI KFT, while network pharmacology analysis indicated a strong interaction between polyphenols and several genes (CASPs, ILs, AGTR1, AKT, ACE2, SOD1, etc.) involved in the pathophysiology of kidney disease. In vivo studies showed a significant (p < 0.05) ameliorative effect on biochemical markers and antioxidant enzymes (SOD, CAT, GSH, etc.), and regulates inflammatory cytokine (TNF-α, IL-1ß, CASP-3) expression in kidney tissue. Hence, it can be concluded that NEERI KFT subsequently alleviates renal dysfunction mediated by cisplatin via attenuating oxidative and inflammatory stress, thus preserving the normalcy of kidney function.

Metabolite profiling and nephroprotective potential of Glycyrrhiza glabra L. roots against cisplatin-induced nephrotoxicity in vitro and in vivo.

Objectives: The present study was conducted to investigate the phytochemical analysis and demonstrate the nephroprotective potential of root extract of Glycyrrhiza glabra L. against cisplatin (CP) -induced nephrotoxicity in vitro and in vivo. Materials and Methods: The HPTLC analysis and UPLC-MS were carried out for standardizing and metabolite profiling of methanolic extract of roots of G. glabra (GGE). Further, in vitro studies were conducted in human embryonic kidney (HEK)-293 cells to evaluate the cytotoxicity and anti-oxidant potential of GGE with CP as a toxicant and ascorbic acid as standard. Also, in vivo nephroprotective potential at doses of 31.5, 63, and 126 mg/kg/day on CP (6 mg/kg, bw, IP) induced nephrotoxicity was evaluated on rodents. Results: Phytochemical analysis by HPTLC and UPLC-MS revealed the presence of glycyrrhizin, glabridin, and liquiritin along with other bioactive constituents. The in vitro assay of GGE showed significant (P<0.001 nephroprotective, cellular anti-oxidant potential and improvement in morphological changes induced by CP. Further, administration of CP caused significant (P<0.001) elevation in biochemical, inflammatory, oxidative stress, caspase-3, as well as histopathological changes in kidney tissue. Pre-treatment with GGE attenuated the elevated biochemical markers significantly, improved histopathological damage, and showed a comparable result to ascorbic acid and α-ketoanalogue. Conclusion: Present study concluded the nephroprotective potential of GGE which supports the traditional claim of G. glabra roots in various kidney and its related disorders. The nephroprotective activity may be attributed to its anti-oxidant, anti-inflammatory, and anti-apoptosis effects. Thus, it holds promising potential in management of nephrotoxicity.

Metabolite Profiling and Nephroprotective Potential of the Zea mays L. Silk Extract against Diclofenac-Induced Nephrotoxicity in Wistar Rats.

The lack of sufficient scientific evidence prompted the analytical investigation of nephroprotective potential of the silk extract of Zea mays L., which is traditionally and ethnomedicinally used for various disorders including kidney dysfunction. The present study was conducted to investigate the phytochemical analysis and demonstrate the nephroprotective potential of the methanolic silk extract of Z. mays L. using a rodent model. High-performance thin-layer chromatography (HPTLC) analysis was carried out to standardize the methanolic silk extract of Z. mays (ZME) using naringenin as a marker. The metabolite profiling of the ZME was carried out using ultrahigh-performance liquid chromatography mass spectrometry (UPLC-MS) on a monolithic capillary silica-based C18 column to identify bioactive compounds and for confirmation of the identified markers. Furthermore, for acute toxicity study, a single dose (2000 mg/kg bw) of the ZME was administered orally to Wistar rats. Also, nephrotoxicity was induced in Wistar rats by injecting diclofenac (DC) (50 mg/kg, bw, i.p.) at a single dose. The efficacy of the ZME as a nephroprotective agent was then evaluated at doses of 100, 200, and 400 mg/kg/day, bw, p.o. Furthermore, the kidney, liver, antioxidant, inflammatory, and apoptotic biochemical markers and histopathological and immunohistochemical alterations (caspase-3 and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4 (NOX-4)) were evaluated. Phytochemical analysis by HPTLC and UPLC-MS revealed the presence of naringenin, vanillic acid, ferulic acid, gallic acid (GA), ellagic acid, quercetin, and morin, along with other bioactive constituents exhibiting multiple pharmacological properties. The acute toxicity study of the ZME showed no mortality or any clinical signs of toxicity through all the 14 days of the toxicity study at a dose of 2000 mg/kg. Also, administration of DC caused a significant elevation (P < 0.001) in kidney biochemical parameters and also caused oxidative, inflammatory, and apoptotic stress. Furthermore, DC also caused histopathological and immunohistochemical changes. Pretreatment with the ZME attenuated the elevated biochemical markers significantly at medium and high doses along with improvement in histopathological and immunohistochemical damages and showing comparable results to those of α-ketoanalogue. The present study verifies the traditional claims of Z. mays silk alleviating various kidney and related disorders by concluding the nephroprotective potential of the ZME. The nephroprotective activity of the ZME is attributed to the phytoconstituents present, acting as potent restoring antioxidants and preventing inflammatory and apoptotic cellular damages in rats. Thus, it holds promising potential in the management of nephrotoxicity.

Heartwood Extract of Pterocarpus marsupium Roxb. Offers Defense against Oxyradicals and Improves Glucose Uptake in HepG2 Cells.

Diabetes mellitus leads to cellular damage and causes apoptosis by oxidative stress. Heartwood extract of Pterocarpus marsupium has been used in Ayurveda to treat various diseases such as leprosy, diabetes, asthma, and bronchitis. In this study, we worked out the mechanism of the antidiabetic potential of methanolic heartwood extract of Pterocarpus marsupium (MPME). First, metabolic profiling of MPME was done using gas chromatography-mass spectrometry (GCMS), ultra-performance liquid chromatography-mass spectroscopy (UPLC-MS), and high-performance thin-layer chromatography (HPTLC) to identify phenols, flavonoids, and terpenoids in MPME. Biological studies were carried out in vitro using the HepG2 cell line. Many antidiabetic compounds were identified including Quercetin. Methanolic extract of MPME (23.43 µg/mL-93.75 µg/mL) was found to be safe and effective in reducing oxyradicals in HepG2 cells. A concentration of 93.75 µg/mL improved glucose uptake efficiently. A significant decrease in oxidative stress, cell damage, and apoptosis was found in MPME-treated HepG2 cells. The study suggests that the heartwood of Pterocarpus marsupium offers good defense in HepG2 cells against oxidative stress and improves glucose uptake. The results show the significant antidiabetic potential of MPME using a HepG2 cell model. The effect seems to occur by reducing oxidative stress and sensitizing the cells towards glucose uptake, hence lowering systemic glucose levels, as well as rescuing ROS generation.

Nutritional constituents of mulberry and their potential applications in food and pharmaceuticals: A review.

Mulberry is a fast growing deciduous plant found in wide variety of climatic, topographical and soil conditions, and is widely distributed from temperate to subtropical regions. Due to presence of valuable phytochemical constituents, mulberry as a whole plant has been utilized as a functional food since long time. Mulberry fruits are difficult to preserve as they have relatively high water content. Therefore for proper utilization, different value-added products like syrups, squashes, teas, pestil sand köme, pekmez (turkuish by-products), yogurts, jams, jellies, wines, vinegar, breads, biscuits, parathas, and many more are made. In overseas, these value-added products are commercially sold and easily available, though in India, this versatile medicinal plant is still missing its identity at commercial and industrial scale. Leaves of mulberry are economically viable due to their important role in the sericulture industry since ancient times. Mulberries or its extracts exhibit excellent anti-microbial, anti-hyperglycaemic, anti-hyperlipidemic, anti-inflammatory, anti-cancer effects and is used to combat different acute and chronic diseases. Different parts of Morus species like fruits, leaves, twigs, and bark exhibit strong anti-tyrosinase inhibition activity that makes it a suitable candidate in cosmetic industries as a whitening agent. The current review provides a comprehensive discussion concerning the phytochemical constituents, functionality and nutraceutical potential of mulberry and as a common ingredient in various cosmetic products.