Modulation of glucose metabolism-related genes in diabetic rats treated with herbal synthetic anti-diabetic compound (α-HSA): insights from transcriptomic profiling.

OBJECTIVES: Eugenia jambolana is a medicinal plant traditionally used for treating diabetes. The bioactive compound FIIc, which is derived from the fruit pulp of E. jambolana, has been identified and purified as α-HSA. Previous studies have demonstrated that administration of α-HSA for 6 weeks improved glycemic index and dyslipidemia in rats with T2D. This study investigated the molecular mechanism underlying the potential therapeutic effects of α-HSA in experimentally induced diabetic rats. METHODS: Male Wistar rats were divided into four groups: diabetic control, diabetic treated with FIIc, diabetic treated with α-HSA, and diabetic treated with glibenclamide. Over a 6-week experimental period, transcriptomic analysis was conducted on liver, skeletal, and pancreatic tissue samples collected from the rats. RESULTS: The study findings revealed significant upregulation of genes associated with glucose metabolism and insulin signaling in the groups treated with FIIc and α-HSA, compared to the diabetic control group. Moreover, pro-inflammatory genes were downregulated in these treatment groups. These results indicate that α-HSA has the potential to modulate key metabolic pathways, improve glucose homeostasis, enhance insulin sensitivity, and alleviate inflammation. CONCLUSIONS: This study provides compelling scientific evidence supporting the potential of α-HSA as a therapeutic agent for diabetes treatment. The observed upregulation of genes related to glucose metabolism and insulin signaling, along with the downregulation of pro-inflammatory genes, aligns with the pharmacological activity of α-HSA in controlling glucose homeostasis and improving insulin sensitivity. These findings suggest that α-HSA holds promise as a novel therapeutic approach for managing diabetes and its associated complications.

Effect of Succinamic Acid Derivative on the Growth Kinetics and Induction of Apoptosis in a Cancer Cell Line.

Introduction Head and neck cancers are heterogeneous malignancies associated with significant morbidity. Oral cancers are related to the use of tobacco products. Smokeless tobacco usage is a health problem worldwide, and its carcinogenic mechanism is largely unknown. Despite advances in conventional treatments, side effects and drug resistance remain unsolved. Therefore, novel therapeutic agents with minimal side effects using plant derivatives should be explored. An active antihyperglycemic and antioxidant compound known as FIIc was isolated from the fruit pulp of Eugenia jambolana (US Patent No.: 2,30,753). Although E. jambolana is reported to have anticancer activity, no study has been reported on its growth kinetics and apoptotic potential in the human head and neck cancer cell line (SCC4). The present study evaluated the effect of an herbal compound isolated from the fruit pulp of E. jambolana and chemically synthesized the same compound, α-hydroxy succinamic acid (α-HSA), on SCC4 proliferation and apoptotic gene expression. Methods The SCC4 cell line was cultured in Dulbecco's Modified Eagle Medium (DMEM). The dosages of smokeless tobacco extract (STE), herbal compound, and synthetic compound were determined by cell viability assay, and their effect on mRNA expression of apoptotic genes was measured by real-time polymerase chain reaction. Results The present study observed significant therapeutic effects of the natural and synthetic compounds from the fruit pulp of E. jambolana at the concentration range of 100-200 µg/mL on the SCC4 cell line. α-HSA had antiproliferative action; upregulated apoptotic genes like p53, p21, and Bax; and downregulated anti-apoptotic genes like survivin in the SCC4 cell line. Conclusion The therapeutic potential of α-HSA and the putative mechanisms involved may be explored to provide the basis for future therapeutic interventions in oral cancer mediated by smokeless tobacco.

Chemokines: A Potential Therapeutic Target to Suppress Autoimmune Arthritis.

BACKGROUND: Chemokines are a family of low molecular weight proteins that induce chemotaxis of inflammatory cells, which mainly depends on the recognition of a chemo-attractant gradient and interaction with the substratum. In Rheumatoid Arthritis (RA), abundant chemokines are expressed in synovial tissue, cause inflammatory cells migration into the inflamed joint that necessitates the formation of new blood vessels i.e. angiogenesis. Over the decades, studies showed that continuous inflammation may lead to the loss of tissue architecture and function, causing severe disability and cartilage destruction. In spite of the advancement of modern drug therapy, thousands of arthritic patients suffer mortality and morbidity globally. Thus, there is an urgent need for the development of novel therapeutic agents for the treatment of RA. METHODS: This review is carried out throughout a non-systematic search of the accessible literature, will provide an overview of the current information of chemokine in RA and also exploring the future perspective of the vital role of targeting chemokine in RA treatment. RESULTS: Since, chemokines are associated with inflammatory cells/leucocyte migration at the site of inflammation in chronic inflammatory diseases and hence, blockade or interference with chemokines activity showing a potential approach for the development of new anti-inflammatory agents. Currently, results obtained from both preclinical and clinical studies showed significant improvement in arthritis. CONCLUSION: This review summarizes the role of chemokines and their receptors in the pathogenesis of RA and also indicates possible interactions of chemokines/receptors with various synthetic and natural compounds that may be used as a potential therapeutic target in the future for the treatment of RA.