Tetrastigma hemsleyanum polysaccharide ameliorated ulcerative colitis by remodeling intestinal mucosal barrier function via regulating the SOCS1/JAK2/STAT3 pathway.

Ulcerative colitis (UC) is characterized by a chronic and protracted course and often leads to a poor prognosis. Patients with this condition often experience postoperative complications, further complicating the management of their condition. Tetrastigma hemsleyanum polysaccharide (THP) has demonstrated considerable potential as a treatment for inflammatory bowel disease. However, its underlying mechanism in the treatment of UC remains unclear. This study systematically and comprehensively investigated the effects of THP on dextran sulfate-induced UC mice and illustrated its specific mechanism of action. The colon and spleen in UC mice were restored after THP treatment. The levels of key markers, such as secretory immunoglobulin A, ß-defensin, and mucin-2 were increased, collagen deposition and epithelial cell apoptosis were decreased. Notably, THP administration led to increased levels of Ki67 and tight junction proteins in colon tissue and reduced colon tissue permeability. THP contributed to the restored balance of intestinal flora. Furthermore, THP downregulated the expressions of the proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17 and promoted those of the regulatory factors forkhead box protein P3. It also exerted anti-inflammatory effects by promoting suppressor of cytokine signaling (SOCS1) expression and inhibiting the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Our results demonstrated that THP had an efficacy comparable to that of JAK inhibitor in treating UC. In addition, THP might play a role in UC therapy through modulation of the SOCS1/JAK2/STAT3 signaling pathway and remodeling of the intestinal mucosal barrier.

Tetrastigma hemsleyanum polysaccharides alleviate imiquimod-induced psoriasis-like skin lesions in mice by modulating the JAK/STAT3 signaling pathway.

BACKGROUND: The pathogenesis of psoriasis involves the interaction between keratinocytes and immune cells, leading to immune imbalance. While most current clinical treatment regimens offer rapid symptom relief, they often come with significant side effects. Tetrastigma hemsleyanum polysaccharides (THP), which are naturally nontoxic, possess remarkable immunomodulatory and anti-inflammatory properties. METHODS: In this study, we utilized an imiquimod (IMQ)-induced psoriasis mouse model and a LPS/IL-6-stimulated HaCaT model. The potential and mechanism of action of THP in psoriasis treatment were assessed through methods including Psoriasis Area Severity Index (PASI) scoring, histopathology, flow cytometry, immunoblotting, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Percutaneous administration of THP significantly alleviated symptoms and manifestations in IMQ-induced psoriatic mice, including improvements in psoriatic skin appearance (erythema, folds, scales), histopathological changes, decreased PASI scores, and spleen index. Additionally, THP suppressed abnormal proliferation of Th17 cells and excessive proliferation and inflammation of keratinocytes. Furthermore, THP exhibited the ability to regulate the JAK/STAT3 signaling pathway. CONCLUSION: Findings from in vivo and in vitro studies suggest that THP can inhibit abnormal cell proliferation and excessive inflammation in lesional skin, balance Th17 immune cells, and disrupt the interaction between keratinocytes and Th17 cells. This mechanism of action may involve the modulation of the JAK/STAT3 signaling pathway, offering potential implications for psoriasis treatment.

Tetrastigma hemsleyanum polysaccharide ameliorates cytokine storm syndrome via the IFN-γ-JAK2/STAT pathway.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an disease characterized by pulmonary edema and widespread inflammation, leading to a notably high mortality rate. The dysregulation of both pro-inflammatory and anti-inflammatory systems, results in cytokine storm (CS), is intricately associated with the development of ALI/ARDS. Tetrastigma hemsleyanum polysaccharide (THP) exerts remarkable anti-inflammatory and immunomodulatory effects against the disease, although its precise role in pathogenesis remains unclear. In the present study, an ALI/ARDS model was established using bacterial lipopolysaccharides. THP administration via aerosol inhalation significantly mitigated lung injury, reduced the number of inflammatory cells, and ameliorated glycerophospholipid metabolism. Furthermore, specific CS-related pathways were investigated by examining the synergy between tumor necrosis factor-α and interferon-γ used to establish CS models. The results indicated that THP effectively decreased inflammatory damage and cell death. The RNA sequencing revealed the involvement of the Janus kinase (JAK) 2-signal transducers and activators of transcription (STAT) signaling pathway in exerting the mentioned effects. Additionally, THP inhibited the activation of the JAK-STAT pathway, thereby alleviating the CS both in vivo and in vitro. Overall, THP exhibited marked therapeutic potential against ALI/ARDS and CS, primarily by targeting the IFN-γ-JAK2/STAT signaling pathway.

A glucuronogalactomannan isolated from Tetrastigma hemsleyanum Diels et Gilg: Structure and immunomodulatory activity.

A novel acidic glucuronogalactomannan (STHP-5) was isolated from the aboveground part of Tetrastigma hemsleyanum Diels et Gilg with a molecular weight of 3.225 × 105 kDa. Analysis of chain conformation showed STHP-5 was approximately a random coil chain. STHP-5 was composed mainly of galactose, mannose, and glucuronic acid. Linkages of glycosides were measured via methylation analysis and verified by NMR. In vitro, STHP-5 induced the production of nitric oxide (NO) and secretion of IL-6, MCP-1, and TNF-α in RAW264.7 cells, indicating STHP-5 had stimulatory activity on macrophages. STHP-5 was proven to function as a TLR4 agonist by inducing the secretion of secreted embryonic alkaline phosphatase (SEAP) in HEK-Blue™-hTLR4 cells. The TLR4 activation capacity was quantitatively measured via EC50, and it showed purified polysaccharides had stronger effects (lower EC50) on activating TLR4 compared with crude polysaccharides. In conclusion, our findings suggest STHP-5 may be a novel immunomodulator.

Ameliorating role of Tetrastigma hemsleyanum polysaccharides in antibiotic-induced intestinal mucosal barrier dysfunction in mice based on microbiome and metabolome analyses.

The intestinal mucosal barrier is one of the important barriers to prevent harmful substances and pathogens from entering the body environment and to maintain intestinal homeostasis. This study investigated the reparative effect and possible mechanism of Tetrastigma hemsleyanum polysaccharides (THP) on ceftriaxone-induced intestinal mucosal damage. Our results suggested that THP repaired the mechanical barrier damage of intestinal mucosa by enhancing the expression of intestinal tight junction proteins, reducing intestinal mucosal permeability and improving the pathological state of intestinal epithelial cells. Intestinal immune and chemical barrier was further restored by THP via the increment of the body's cytokine levels, intestinal SIgA levels, intestinal goblet cell number, intestinal mucin-2 levels, and short-chain fatty acid levels. In addition, THP increased the abundance of probiotic bacteria (such as Lactobacillus), reduced the abundance of harmful bacteria (such as Enterococcus) to repair the intestinal biological barrier, restored intestinal mucosal barrier function, and maintains intestinal homeostasis. The possible mechanisms were related to sphingolipid metabolism, linoleic acid metabolism, and D-glutamine and D-glutamate metabolism. Our results demonstrated the potential therapeutic effect of THP against intestinal flora disorders and intestinal barrier function impairment caused by antibiotics.

Polysaccharides from Tetrastigma Hemsleyanum Diels et Gilg ameliorated inflammatory bowel disease by rebuilding the intestinal mucosal barrier and inhibiting inflammation through the SCFA-GPR41/43 signaling pathway.

In this study, the therapeutic effects of Tetrastigma hemsleyanum polysaccharide (THP) on inflammatory bowel disease (IBD) and its possible mechanisms were investigated based on the IBD mouse model induced by dextran sodium sulfate (DSS) and the lipopolysaccharide (LPS)-stimulated Caco-2 cell model. THP significantly alleviated the signs and symptoms of DSS-induced IBD mice, including the reduced weight, shortened colonic length, and increased colitis disease activity index. In vivo, THP significantly reduced inflammatory cell infiltration and oxidative damage, promoted intestinal mucus secretion, and restored the integrity of the intestinal epithelial barrier and mucus barrier. Furthermore, THP reversed the changes in the intestinal flora of colonized mice and restored the levels of short-chain fatty acids (SCFAs) by increasing the abundance of potentially beneficial bacteria and increasing the abundance of butyrate-producing bacteria. In addition, THP upregulated the expression of G-protein-coupled receptors (GPR41 and GPR43) both in vivo and in vitro. In summary, the current investigation showed that THP effectively protected against intestinal inflammation and impairment in the intestinal barrier in the setting of DSS-induced IBD, possibly by regulating gut microbiota structure and corresponding SCFA metabolites, and the pathway of SCFAs action may be related to SCFA-GPR41/43 signaling pathway.