Exploring aryl hydrocarbon receptor (AhR) as a target for Bisphenol-A (BPA)-induced pancreatic islet toxicity and impaired glucose homeostasis: Protective efficacy of ethanol extract of Centella asiatica.

The estrogenic impact of Bisphenol-A (BPA), a widely recognized endocrine disruptor, causes disruption of pancreatic ß-cell function through estrogen receptors (ERs). While BPA's binding affinity for ERs is significantly lower than that of its natural counterpart, estrogen, recent observations of BPA's affinity for aryl hydrocarbon receptor (AhR) in specific cellular contexts have sparked a specific question: does AhR play a role in BPA's toxicological effects within the endocrine pancreas? To explore this question, we investigated BPA's (10 and 100 µg/ kg body weight/day for 21 days) potential to activate AhR within pancreatic islets and assessed the protective role of ethanol extract of Centella asiatica (CA) (200 and 400 mg/kg body weight/day for 21 days) against BPA-mediated toxicity in mouse model. Our results indicate that BPA effectively triggers the activation of AhR and modulates its target genes within pancreatic islets. In contrast, CA activates AhR but directs downstream pathways differentially and activates Nrf2. Additionally, CA was observed to counteract the disruption caused by BPA in glucose homeostasis and insulin sensitivity. Furthermore, BPA-induced oxidative stress and exaggerated production of proinflammatory cytokines were effectively counteracted by CA supplementation. In summary, our study suggests that CA influenced AhR signaling to mitigate the disrupted pancreatic endocrine function in BPA exposed mice. By shedding light on how BPA interacts with AhR, our research provides valuable insights into the mechanisms involved in the diabetogenic actions of BPA.

Protective efficacy of Tinospora sinensis against streptozotocin induced pancreatic islet cell injuries of diabetic rats and its correlation to its phytochemical profiles.

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora sinensis Lour. (Merr.) belongs to the family Menispermaceae and its stem extract have been used traditionally in broad aspects of therapeutic remedies including debility, dyspepsia, fever, jaundice, ulcer, bronchitis, urinary disease, skin disease, liver disease and diabetes. AIM OF THE STUDY: The aim of the study was to evaluate the protective effects of methanol extract of stem of Tinospora sinensis (METS) on streptozotocin induced pancreatic islet cell injuries of diabetic rats and its correlation to its phytochemical profiles. MATERIALS AND METHODS: A high-performance liquid chromatography technique (HPLC) was used to identify and quantify the major phytochemicals present in the METS. Diabetic rats were administered with METS at a dose of (100, 200 and 400 mg/kg respectively orally) and standard drug Metformin (300 mg/kg) was given orally to group serving positive control. Effect of the METS on glucose homeostasis, oxidative stress, antioxidant status, histopathology of pancreas and also on intracellular reactive oxygen species (ROS), mitochondrial membrane potential, apoptosis, cell cycle of pancreatic islet cells were studied in diabetic rats. RESULTS: The major phytochemicals identified and quantified by HPLC in the extract were berberine, caffeic acid, myricetin and ferulic acid. This result showed that methanol extract exhibited good antioxidant effect. The methanol extract of the plant prevented the diabetogenic effect of STZ and significantly lowered the fasting blood glucose level, glycated haemoglobin and increased insulin and C-peptide level in treated rats. METS reduced apoptosis of STZ treated islet cells by significantly decreasing pro-inflammatory cytokines (TNFα, IL6), intracellular ROS generation, lipid peroxidation, nitric oxide (NO) production and increasing mitochondrial membrane potential and sub-G0 peak area, enzymatic and nonenzymatic antioxidants. CONCLUSION: The results revealed that the methanol extract of the stem of the plant possesses protective effects against diabetes and associated complications.

High frequency direct shoot organogenesis of leaf explants and a comparative evaluation of phytochemicals, antioxidant potential of wild vs. in vitro plant extracts of Lysimachia laxa.

The present studies were attempted to develop direct shoot organogenesis from in vitro grown leaf explants of Lysimachia laxa and comparative evaluation of phytochemical and antioxidant potential of in vitro raised and wild plants extracts. The fresh leaves of this species are used for deworming gastrointestinal worm infection in traditional medicine. Overexploitation of this species and poor regeneration has led to rapid decline in wild population, therefore, present investigation was attempted to develop an efficient rapid mass propagation protocol for this species. Our result showed significantly (P < 0.05) high adventitious shoot proliferation of 17.21 ± 0.24 number per leaf explants cultured in Murashige and Skoog medium fortified with 1.25 mg L-1 thiadizuron and 1.0 mg L-1 α-naphthalene acetic acid. Further enhancement was achieved through elongation medium fortified with 1.0 mg L-1 6-benzylaminopurine by average shoot number of 31.1 ± 0.80 and length of 5.96 ± 0.13 cm. Murashige and Skoog medium fortified with 0.50 mg L-1 Indole-3-acetic acid showed high rooting induction (100%) with average root number of 11.70 and length 7.35 cm. All rooted plants were successfully acclimatized in greenhouse and transferred to field condition with a survival rate of 97%. The contents of phenolic and flavonoid were higher in in vitro raised plant in compared to wild plant extracts. Antioxidants assay showed high radical scavenging activity of IC50 1.61 ± 0.07 mg dry material and reducing power of 49.79 ± 0.11 mg/g ascorbic acid equivalent by aqueous methanol extracts of in vitro raised 3-months-old plants in compare to the wild plants. The present protocol is a viable option for pharmaceutical or nutraceutical industries for sustainable utilization of L. laxa with enhanced of phytochemical and antioxidant potency which is not reported elsewhere.

Evaluation of Cynodon dactylon for wound healing activity.

BACKGROUND AND AIMS: Research in the field of wound healing is very recent. The concept of wound healing is changing from day to day. Ayurveda is the richest source of plant drugs for management of wounds and Cynodon dactylon L. is one such. The plant is used as hemostatic and wound healing agent from ethnopharmacological point of view. Aim of the present study is scientific validation of the plant for wound healing activity in detail. MATERIALS AND METHODS: Aqueous extract of the plant was prepared and phytochemical constituents were detected by HPLC analysis. Acute and dermatological toxicity study of the extract was performed. Pharmacological testing of 15% ointment (w/w) of the extract with respect to placebo control and standard comparator framycetin were done on full thickness punch wound in Wister rats and effects were evaluated based on parameters like wound contraction size (mm2), tensile strength (g); tissue DNA, RNA, protein, hydroxyproline and histological examination. The ointment was applied on selected clinical cases of chronic and complicated wounds and efficacy was evaluated on basis of scoring on granulation, epithelialization, vascularity as well as routine hematological investigations. RESULTS: Significant results (p<0.05) were observed both in pharmacological and clinical studies. CONCLUSION: The present research with aqueous extract of Cynodon dactylon explores its potential wound healing activity in animal model and subsequent feasibility in human subjects. Phenolic acids and flavonoids present in c. dactylon supports its wound healing property for its anti-oxidative activity that are responsible for collagenesis.

Antidiabetic activity of Caesalpinia bonducella F. in chronic type 2 diabetic model in Long-Evans rats and evaluation of insulin secretagogue property of its fractions on isolated islets.

Caesalpinia bonducella F., is a shrub widely distributed throughout the coastal region of India and is ethnically used by the tribal people of Andaman and Nicober Island as a remedy of symptoms of diabetes mellitus. This ethnic report prompted the detail investigation of hypoglycemic activity of Caesalpinia bonducella seeds, initially on physiological hyperglycemic model and then on type 1 and type 2 sub-acute diabetic animal models which has already been reported. Evaluation of different extracts from Caesalpinia bonducella in chronic type 2 diabetic model alongwith insulin secretagogue activity of five fractions isolated from the Caesalpinia bonducella seed kernel are presented in this paper. Both the aqueous and ethanolic extracts showed potent hypoglycemic activity in chronic type 2 diabetic model. Two fractions BM 169 and BM 170 B could increase secretion of insulin from isolated islets.

(+)-Tiliarine, a selective in vitro inhibitor of human melanoma cells.

Five diphenylbisbenzylisoquinoline (DBBI) alkaloids, tiliacorinine, tiliacorine, nor- tiliacorinine A, tiliarine and tiliamosine were isolated from the ethanol extract of the roots of Tiliacora racemosa Colebr. and identified by spectral techniques. Of these (+)-tiliarine is the only one which exhibited a selective inhibitory effect against human melanoma cells (G 361) and had no activity on normal human fibroblasts (CCD 974 SK). The activity of (+)-tiliarine against the human melanoma cell line was not much modified in the presence of calcium chloride.