Polyherbal extract improves glycometabolic control in alloxan-induced diabetic rats via down-regulating the MAPK/JNK pathway, modulating Nrf-2/Keap-1 expression, and stimulating insulin signaling.

Objectives: This study focused on the evaluation of antioxidant and antidiabetic activities of polyherbal extract (PHE), containing Cassia absus (L.), Gymnema sylvestre (R. Br.), Nigella sativa (L.), and Piper nigrum (L.), in alloxan-induced diabetes model. Materials and Methods: In vitro, HPLC characterization, DPPH scavenging assay, and α-amylase inhibition test were conducted. In vivo, acute oral toxicity of PHE was assessed. Alloxan-induced diabetic Wistar rats (n=6) were orally treated with PHE (200, 400, and 600 mg/kg/day) and glibenclamide (GLB; 10 mg/kg/day) for six consecutive weeks. Then, biochemical biomarkers, oxidative stress parameters, histopathological examination, and mRNA expression levels (RT-qPCR) were determined. Results: The presence of polyphenols in PHE was confirmed in correlation to marked DPPH scavenging (IC50: 1.60 mg/ml) and α-amylase inhibition (IC50: 0.82 mg/ml). PHE demonstrated no toxicity in rats up to a dose of 2000 mg/kg. In diabetic rats, PHE dose-dependently ameliorated the serum levels of glucose, insulin, glycated hemoglobin A1c (HbA1c), leptin, and glucokinase (GCK). Also, PHE substantially alleviated serum inflammatory markers (TNF-α and CRP) and oxidative stress indicators (MDA, SOD, and CAT) in pancreatic tissues. PHE, particularly at 600 mg/kg, attenuated cellular oxidative stress via modulating the mRNA expression levels of genes regulating MAPK/JNK (Mapk-8, Traf-4, and Traf-6) and Nrf-2/Keap-1 pathways and promoted insulin signaling through up-regulating insulin signaling cascade (Pdx-1, Ins-1, and Ins-2), as compared to GLB. Furthermore, histopathological findings supported the aforementioned results. Conclusion: Our study suggests that polyherbal extract has promising antioxidant and antidiabetic activities by modulating the MAPK/JNK, Nrf-2/Keap-1, and insulin signaling pathways.

Effect of a polyherbal formulation on L-thyroxine induced hyperthyroidism in a rat model: In vitro and in vivo analysis and identification of bioactive phytochemicals.

An excess of thyroid hormones in the blood characterizes hyperthyroidism. Long-term use of prescription medications to treat hyperthyroidism has substantial adverse effects and when discontinued, the symptoms frequently recur. Several plant species have been utilized to cure hyperthyroidism. In the present work, we investigated the impact of polyherbal extract (POH) of four medicinal plants to treat hyperthyroidism. Biochemical analysis revealed the presence of a high concentration of phytochemicals in the POHs. The in vitro antioxidant study revealed their antioxidant and free radical scavenging capacity. The gas chromatography coupled mass spectrometry analysis of the POHs showed the presence of 13 bioactive phytochemical compounds. The effect of various concentrations of POHs on L-thyroxine-induced hyperthyroidism in Wistar albino rats was evaluated for 18 days. The TSH, T3 and T4 levels increased significantly and reduced the increase of liver enzymes caused by hyperthyroidism in POH-treated rats. The data showed that POH therapy could restore thyroid function to normal. The injection of POH increased the size comprising vacuolated cells, columnar follicular cells and highly coloured nuclei with increasing POH content and the number of normal thyroid follicles rose. The findings indicate that polyherbal formulations of these medicinal plants include credible antithyroid compounds that may offer a protective and an effective alternative treatment to synthetic thyroid medications.

Phytochemicals, Antioxidant, Anti-inflammatory Studies, and Identification of Bioactive Compounds Using GC-MS of Ethanolic Novel Polyherbal Extract.

Hyperglycemia is the hallmark of diabetes, which is a collection of related metabolic disorders. Over time, diabetes can cause a variety of problems, including cardiovascular disease, nephropathy, neuropathy, and retinopathy. Ethanolic novel polyherbal extract (PHE) was prepared by mixing equal amounts of the following ingredients: Terminalia chebula Retz. (TC), Terminalia bellerica Roxb. (TB), Berberis aristata DC. (BA), Nyctanthes arbostratis L. (NA), Premna integrifolia L. (PI), and Andrographis paniculata Nees. (AP). Analysis of PHE results revealed phytochemicals like glycosides, flavonoids, alkaloids, tannins, phytosterols, and saponins. The aim of the study was to prepare an ethanolic extract of PHE using the cold maceration technique, and identify bioactive molecules from gas chromatography-mass spectrometry (GC-MS) analysis, and evaluate biological responses by using in vitro studies like antioxidant and anti-inflammatory activity. PHE was found to contain a total of 35 phytochemicals in GC-MS of which 22 bioactive compounds were obtained in good proportion. There are a few new ones, including 2-buten-1-ol, 2-ethyl-4-(2, 2, 3-trimethyl-3-cyclopenten-1-yl (17.22%), 1, 2, 5, 6-tetrahydrobenzonitrile (4.26%), 4-piperidinamine, 2, 2, 6, 6-tetramethyl-(0.07%), undecanoic acid, 5-chloro-, chloromethyl ester (0.41%), are identified. Antioxidant activity was estimated using EC50 values of 392.143 µg/ml, which were comparable to the standard value of EC50 310.513 µg/ml obtained using DPPH. Antioxidant activity was estimated with EC50 392.143 µg/ml, comparable to standard EC50 310.513 µg/ml using DPPH. In vitro anti-inflammatory potential was found with IC50 of 91.449 µg/ml, comparable to standard IC50 89.451 µg/ml for membrane stabilization and IC50 of 36.940 µg/ml, comparable to standard IC50 35.723 µg/ml for protein denaturation assays. As a result, the findings of this study show an enrichment of bioactive phytochemicals that can be used to investigate biological activity. To better understand how diabetes receptors work, in silico studies like docking could be carried out.

Preclinical evaluation from in-silico to in-vivo study of polyherbal microsponge sunscreen gel.

BACKGROUND: Electromagnetic spectrum of the UV region predominantly becomes the reason for skin's detrimental effects that give the genesis of innumerable skin ailments; because of this reason, the sunscreen products are required before condition in day to day lifestyle; products such as moisturizers, lotions, creams, shampoos, and other hair and skin preparations are accessible and accompanied by sunscreen properties, but they do not provide extended effect, also causes side effects due to harsh chemicals. AIM: The present study focuses on the effects of polyherbal extracts containing Microsponge gel for the protection of skin from ultraviolet rays. MATERIALS AND METHODS: In the present research, already prepared Microsponge gel through quasi-emulsion solvent diffusion (QESD) technique was used for the HPLC, in-silico, in-vitro antioxidant activity, and in-vivo study. AdmetSAR software tool was utilized for the in-silico study, whereas for the in-vivo study, UV radiations are given on Albino rats using solarimeter. RESULTS: Results shown the active constituents are non-carcinogenic and non-toxic; IC50 values show good antioxidant activity and minimal effect of UV radiations after application of the gel formulation on animal skin. DISCUSSION: The results manifest prominent effects on animal skin further test for presence of ascorbic acid level and total protein in blood further verify the efficacy of the formulation. CONCLUSION: The study consequently established a strong ground for further extensive clinical studies.

Improving gallic acid and quercetin bioavailability by polymeric nanoparticle formulation.

The anticancer activity and pharmacokinetic properties of encapsulated polyherbal nanoparticles (gallic acid (GA) and quercetin nanocomposite) and polyherbal extract (amla and pomegranate fruit peels) in normal and DMH-induced colorectal cancer in rats were examined in this work. In normal and DMH-induced rats, a pharmacokinetic study demonstrated that polyherbal nanoparticles had a typical sustained release profile with a fourfold increase in bioavailability when compared to polyherbal extract. Based on serum-concentration profiles of polyherbal nanoparticles and polyherbal extract following oral administration, the pharmacokinetic parameters for polyherbal nanoparticles and polyherbal extract were established using a single compartmental approach. This research suggests that encapsulating GA and quercetin in polymeric nanoparticles improves their oral bioavailability and anti-colon cancer efficacy. Polymeric nanoparticles could be a novel therapeutic possibility for carcinogenesis prevention.

An antidiabetic polyherbal phytomedicine confers stress resistance and extends lifespan in Caenorhabditis elegans.

An Ayurvedic polyherbal extract (PHE) comprising six herbs viz. Berberis aristata, Cyperus rotundus, Cedrus deodara, Emblica officinalis, Terminalia chebula and Terminalia bellirica is mentioned as an effective anti-hyperglycemic agent in 'Charaka Samhita', the classical text of Ayurveda. Previously, antidiabetic drug metformin was found to elicit antiaging effects and PHE was also found to exhibit antidiabetic effects in humans. Therefore, we screened it for its in vivo antioxidant antiaging effect on stress and lifespan using human homologous Caenorhabditis elegans model system. The effect on aging is evaluated by studying effect of PHE on mean survival in worms. The stress modulatory potential was assessed by quantification of intracellular ROS level, autofluorescent age pigment lipofuscin, oxidative and thermal stress assays. Additionally, stress response was quantified using gene reporter assays. The 0.01 µg/ml dose of PHE was able to enhance mean lifespan by 16.09% (P < 0.0001) in C. elegans. Furthermore, PHE treated worms demonstrated oxidative stress resistance in both wild type and stress hypersensitive mev-1 mutant along with upregulation of stress response genes sod-3 and gst-4. The delayed aging under stress can be attributed to its direct reactive oxygen species-scavenging activity and regulation of some age associated genes like daf-2, daf-16, skn-1, sod-3 and gst-4 in wild-type worms. Additonally, PHE delayed age related paralysis phenotype in CL4176 transgenic worms. Altogether, our results suggest PHE significantly improves the oxidative stress and life span in C. elegans. Overall the present study suggests this polyherbal formulation might play important role in regultaing aging and related complications like diabetes.