Argel's stemmoside C as a novel natural remedy for mice with alcohol-induced gastric ulcer based on its molecular mechanistic pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Solenostemma argel is widely distributed in Africa & Asia with traditional usage in alleviating abdominal colic, aches, & cramps. This plant is rich in phytochemicals, which must be explored for its pharmacological effects. PURPOSE: Peptic Ulcer Disease (PUD) is the digestion of the digestive tube. PUD not only interferes with food digestion & nutrient absorption, damages one of the largest defensive barriers against pathogenic micro-organisms, but also impedes drug absorption & bioavailability, rendering the oral route, the most convenient way, ineffective. Omeprazole, one of the indispensable cost-effective proton-pump inhibitors (PPIs) extensively prescribed to control PUD, is showing growing apprehensions toward multiple drug interactions & side effects. Hence, finding a natural alternative with Omeprazole-like activity & limited side effects is a medical concern. STUDY DESIGN: Therefore, we present Stemmoside C as a new gastroprotective phytochemical agent isolated from Solenostemma argel to be tested in upgrading doses against ethanol-induced gastric ulcers in mice compared to negative, positive, & reference Omeprazole groups. METHODS: We carried out in-depth pharmacological & histopathological studies to determine the possible mechanistic pathway. RESULTS: Our results showed that Stemmoside C protected the stomach against ethanol-induced gastric ulcers parallel to Omeprazole. Furthermore, the mechanistic studies revealed that Stemmoside C produced its effect using an orchestrated array of different mechanisms. Stemmoside C stimulates stomach defense by increasing COX-2, PGE-2, NO, & TFF-1 healing factors, IL-10 anti-inflammatory cytokine, & Nrf-2 & HO-1 anti-oxidant pathways. It also suppresses stomach ulceration by inhibiting leucocyte recruitment, especially neutrophils, leading to subsequent inhibition of NF-κBp65, TNF-α, IL-1ß, & iNOS pro-inflammatory cytokines & JAK-1/STAT-3 inflammation-induced carcinogenicity cascade in addition to MMP-9 responsible for tissue degradation. CONCLUSION: These findings cast light on Stemmoside C's clinical application against gastric ulcer progression, recurrence, & tumorigenicity & concurrently with chemotherapy.

Enhanced immune responses in dexamethasone immunosuppressed male rats supplemented with herbal extracts, chitosan nanoparticles, and their conjugates.

Nowadays, the world is challenged with highly contagious diseases, one of their preliminary virulence mechanisms is the suppression of innate immunity. Therefore, promoting natural immunity is a good precautionary strategy. we investigated and compared the effects of several natural herbal extracts -Moringa oleifera, Ziziphus spina christi, and Saussurea costus, and chitosan nanoparticles (CS NPs)- as well as conjugated extracts with CS NPs on the immunological parameters of dexamethasone immunosuppressed (IS) male rats. The plant extracts were assessed for total flavonoids, phenolics, and antioxidant activity. The CS NPs and their conjugates were characterized using particles size, zeta potentials, and Fourier-transform infrared spectroscopy analyses. The chemical analysis of the plant extracts, CS NPs, and their conjugates was performed using energy dispersive X-ray fluorescence, and their cytotoxicity was evaluated in human lung fibroblast (WI-38) and human embryonic kidney (HEK-293) cell lines. For in vivo evaluations, 72 adult male rats were divided into 9 groups: control, IS, three plant extracts, CS, and conjugates of the three plant extracts and CS NPs. Oral supplementation (day after day) lasted for 28 days. Liver, kidney, and spleen tissue samples were collected for histopathology and Ki-67 expression analyses. The results revealed that the plant extracts and CS improved the total leukocyte counts, complement 3, complement 4, interferon-gamma, and tumor necrosis factor levels at day 28. However, the plant extract-CS NPs conjugates faster and have higher immunostimulatory effects at day 14. Furthermore, the atrophied white pulp of the spleen induced by dexamethasone was alleviated, and Ki-67 expression was elevated in all the treated groups. Conclusively, the conjugates of Moringa oleifera, Ziziphus spina christi, and Saussurea costus extract with CS NPs demonstrated more potent and rapid immune responses at lower doses and concentrations compared to the plant extracts or CS NPs alone, without causing liver or kidney injuries. Thus, supplementation of these conjugated plant extracts at lower doses and concentrations is recommended to improve immunity while considering safety considerations.