Oleuropein Enhances Stress Resistance and Extends Lifespan via Insulin/IGF-1 and SKN-1/Nrf2 Signaling Pathway in Caenorhabditis elegans

Oleuropein (OLE) is a secoiridoid glycoside that mainly exists in olives with multifaceted health benefits. The present study aimed to investigate the stress resistance and lifespan extension effects of OLE in Caenorhabditis elegans. The results showed that OLE could significantly prolong the lifespan of C. elegans by 22.29%. Treatment with OLE also significantly increased the survival rates of worms against lethal heat shock and oxidative stress. Meanwhile, OLE supplementation increased the expression and activity of antioxidant enzymes and suppressed the generation of malondialdehyde in nematodes. In addition, the results from mutants implied that OLE might mediate longevity and stress resistance via DAF-16/FoxO, which played a vital role in the insulin/IGF-1 signaling (IIS) pathway. To further identify the molecular targets of OLE, mRNA level and loss-of-function mutants of IIS-associated genes were investigated. The data revealed that OLE activated IIS by down-regulating the upstream components, daf-2 and age-1. Furthermore, another stress response and longevity pathway in parallel to DAF-16, SKN-1/Nrf2, was also shown to involve in OLE-induced beneficial effects. Collectively, these results provide the theoretical basis that OLE could enhance the stress resistance and increase the lifespan of C. elegans through the IIS and SKN-1/Nrf2 signaling pathways.

Gentiopicroside, a Secoiridoid Glycoside from Gentiana rigescens Franch, Extends the Lifespan of Yeast via Inducing Mitophagy and Antioxidative Stress

Gentiopicroside (GPS), an antiaging secoiridoid glycoside, was isolated from Gentiana rigescens Franch, a traditional Chinese medicine. It prolonged the replicative and chronological lifespans of yeast. Autophagy, especially mitophagy, and antioxidative stress were examined to clarify the mechanism of action of this compound. The free green fluorescent protein (GFP) signal from the cleavage of GFP-Atg8 and the colocation signal of MitoTracker Red CMXRos and GFP were increased upon the treatment of GPS. The free GFP in the cytoplasm and free GFP and ubiquitin of mitochondria were significantly increased at the protein levels in the GPS-treated group. GPS increased the expression of an essential autophagy gene, ATG32 gene, but failed to extend the replicative and chronological lifespans of ATG32 yeast mutants. GPS increased the survival rate of yeast under oxidative stress condition; enhanced the activities of catalase, superoxide dismutase, and glutathione peroxidase; and decreased the levels of reactive oxygen species and malondialdehyde. The replicative lifespans of Δsod1, Δsod2, Δuth1, and Δskn7 were not affected by GPS. These results indicated that autophagy, especially mitophagy, and antioxidative stress are involved in the antiaging effect of GPS.

Secoiridoid Amarogentin from ‘Gentianaceae’ with their Health Promotion, Disease Prevention and Modern Analytical Aspects

Background: Plant-based products and their derivatives have been widely used in the medicine, nutraceuticals, and the cosmetic and pharmaceutical field for a very long time. A large number of important drugs of modern medicine have also been derived from the plant's sources. Plant products specifically the pure phytochemical also known as ‘biomarkers’ have been used in the food and pharmaceutical industries. Biomarker compounds are pure phytochemical and they are mainly responsible for various pharmacological activities of plant material and examples of biomarker are Amarogentin, Vasicine, Hyoscyamine and Paclitaxel. Methods: Various literature databases were searched to collect important information about Amarogentin in this review. Ethnomedicinal uses, pharmacological activities, phytochemical aspects and modern analytical tools of amarogentin were presented and discussed. Further, all the collected information’s were categorized into different section as per the need of the manuscripts. Moreover, data were also presented in the graphical abstract, Figures and Table section too. Results: Swertia chirata (S. chirata) is a common plant of Gentianaecae family which is mainly known for their bitter taste. Gentiopicroside, amarogentin, swertiamarin, isovitexin and isogentisin are some important phytoconstituents of S. chirata. Decoction, infusion, pastes and juice of S. chirata are basically used in the medicine. Various Pharmacological activities such as hypoglycemic, antimicrobial, antimalarial, antihepatotoxic, anticarcinogenic, antioxidative and anti-inflammatory have been reported in the literature for S. chirata plant. Amarogentin, a bitter secoiridoid glycoside of S. chirata has been well known for antibacterial, anticholinergic anti-lieshmanial, chemopreventive, antihepatitis and anticancer activities. Conclusion: Information provided in the present paper regarding phytochemistry, pharmacological uses and analytical aspects including bioavailability will be beneficial to various disciplines of biological science. Development of plant tissue culture-based approaches is also needed for the proper conservation of S. chirayita plants in the future.

BIOCHEMICAL EVALUATION OF ANTIDIABETIC PROPERTIES OF SWERTIAMARIN, A SECOIRIDOID GLYCOSIDE OF ENICOSTEMMA LITTORALE LEAVES, STUDIED IN HIGH-FAT DIET–FED LOW-DOSE STREPTOZOTOCIN-INDUCED TYPE 2 DIABETIC RATS

Objective: Swertiamarin, a secoiridoid glycoside present in the leaves of Enicostemma littorale, is reported to be responsible for its pharmacological and beneficial properties. The present study was aimed to biochemically evaluate the antidiabetic properties of Swertiamarin in high fat diet fed - low dose streptozotocin (STZ)-treated diabetic rats.Methods: High-fat diet-fed low-dose STZ was used to induce experimental type 2 diabetes in rats. Diabetic rats were orally treated with swertiamarin (50 mg/kg b.w./rat/day) for 30 days. The physiological criterions such as food and fluid intake were recorded. Oral glucose tolerance test was performed. The levels of fasting blood glucose, plasma insulin, glycosylated hemoglobin A1c (HbA1c), hemoglobin, and homeostasis model assessment of insulin resistance (HOMA-IR) values were estimated. The activities of key enzymes involved in carbohydrate and glycogen metabolism in the liver and kidney tissues were assayed. The glycogen content in liver tissue was estimated.Result: Oral administration of swertiamarin to diabetic rats established a significant decline in the levels of fasting blood glucose, HbA1c as well as HOMA-IR values and an increase in plasma insulin and hemoglobin levels. The altered activities of key enzymes of carbohydrate and glycogen metabolism in liver and kidney tissues of diabetic rats were restored to near normalcy by swertiamarin treatment.Conclusion: Swertiamarin treatment maintains normoglycemia in diabetic rats by modulating the activities of key carbohydrate and glycogen metabolizing enzymes in the hepatic and renal tissues.