Aytursun Abuduwaili

Background/Objectives: The worldwide occurrence of ulcerative colitis (UC) is increasing, but existing treatments frequently suffer from limited effectiveness and notable side effects. walnut green husk polysaccharide (WGHP) has been shown to exhibit anti-inflammatory and immunomodulatory activities; however, its specific potential and mechanisms of action against colitis remain unclear. This study aimed to evaluate the effectiveness of purified WGHP on (dextran sulfate sodium) DSS-induced UC and elucidate the underlying mechanisms. Methods: WGHP-2-2, a primary acidic polysaccharide fraction, was extracted from crude WGHP and analyzed through chromatography and spectroscopy. The therapeutic efficacy of WGHP-2 was assessed using a murine model of DSS-induced UC. Assessments included disease severity (DAI, colon length, histopathology), inflammatory markers (tissue IL-6, TNF-α, IL-10), and intestinal barrier integrity (Claudin-5, Occludin, ZO-1). Results: WGHP-2-2 is an acidic polysaccharide with a molecular weight of 15.29 kDa. Its composition includes glucosamine, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose, with respective molar ratios of 0.55, 8.48, 3.06, 65.99, 4.49, 10.86, and 6.57. Methylation and NMR analyses revealed a backbone mainly composed of →4)-α-D-GalpA-(1→ and →2)-α-D-Rhap-(1→ linkages, with side chains or terminal residues such as T-Rhap, T-Galp, T-Glcp, and T-Araf. In vivo, WGHP-2 significantly mitigated DSS-induced UC symptoms in a dose-dependent manner. Specifically, the high-dose group (123 mg/kg) markedly attenuated colon shortening and improved histological architecture, including the restoration of colonic crypts. WGHP-2 effectively reduced pro-inflammatory cytokines IL-6 and TNF-α in colon tissues, while increasing the anti-inflammatory cytokine IL-10. Conclusions: WGHP-2 mitigates DSS-induced UC by inhibiting pro-inflammatory cytokines (IL-6, TNF-α), increasing IL-10 levels, and improving intestinal barrier integrity through the upregulation of tight junction proteins. These results position WGHP-2 as a promising lead compound for developing functional foods for UC.

Acidic polysaccharides, valued for their outstanding bioactivity and physicochemical properties, represent a promising strategy for metabolic disease intervention. In this study, three acidic polysaccharide fractions (BRP-1, BRP-2, and BRP-3) were isolated from Brassica rapa L. using membrane filtration and ion-exchange chromatography. BRP-3, notable for its high galacturonic acid content (76.64%), was further purified to yield the homogeneous fraction BRP-3-1 (Mw = 22.3 kDa). Combining GC-MS, FTIR, and NMR analyses, we report for the first time the detailed structure of BRP-3-1—a heteropolysaccharide composed of rhamnose (1.687%), galacturonic acid (75.584%), galactose (14.452%), and arabinose (8.277%)—with a backbone composed with T-α-L-Araf-(1 → 5)-α-L- Araf -(1 → 4)-α-D-GalpA-(1 → 4)-α-D-2-O- GalpA Me-(1 → 4)-α-D-GalpA-(1 → 4)-α-D-GalpA-(1 → 3)-Galp-(1 → 4)-α-D-GalpA, and T-Rhap, T-Galp as well as T-GalpA for branched chain and terminals. In HepG2 insulin-resistant cells, BRP-3-1 demonstrated potent dual regulation of glucose and lipid metabolism—enhancing glucose consumption, lowering total cholesterol, and significantly reducing triglyceride levels in the high-dose group (800 μg/mL), outperforming BRP-2. This work systematically defines the structure of a highly bioactive acidic polysaccharide from B. rapa L. and confirms its metabolic regulatory effects, offering a strong scientific foundation for its application in functional foods and as an adjuvant therapeutic for metabolic disorders.

Multidrug resistance (MDR) is a central cause of chemotherapy failure and tumor recurrence and metastasis, and its mechanism involves enhanced drug efflux, target mutation, upregulation of DNA repair and remodeling of the tumor microenvironment. ABC transporter protein (P-gp, MRP, and BCRP)-mediated efflux of drugs is the most intensively researched aspect of the study, but the first three generations of small-molecule reversal agents were stopped in the clinic because of toxicity or pharmacokinetic defects. Natural products are considered as the fourth generation of MDR reversal agents due to their structural diversity, multi-targeting and low toxicity. In this paper, we systematically summarize the inhibitory activities of monoterpenes, sesquiterpenes, diterpenes and triterpenes against ABC transporter proteins in in vitro and in vivo models and focus on the new mechanism of reversing drug resistance by blocking efflux pumps, modulating signaling pathways such as PI3K-AKT, Nrf2, NF-κB and remodeling the tumor microenvironment. For example, Terpenoids possess irreplaceable core advantages over traditional multidrug resistance (MDR) reversers: Compared with the first three generations of synthetic reversers, natural/semisynthetic terpenoids integrate low toxicity (mostly derived from edible medicinal plants, half-maximal inhibitory concentration IC₅₀ > 50 μM), high target specificity (e.g., oleanolic acid specifically inhibits the ATP-binding cassette (ABC) transporter subtype ABCC1 without cross-reactivity with ABCB1), and multi-mechanistic synergistic effects (e.g., β-caryophyllene simultaneously mediates the dual effects of “ABCB1 efflux inhibition + apoptotic pathway activation”). These unique characteristics enable terpenoids to effectively circumvent key limitations of traditional synthetic reversers, such as high toxicity and severe drug–drug interactions. Among them, lupane-type derivative BBA and euphane-type sooneuphanone D (triterpenoids), as well as dihydro-β-agarofuran-type compounds and sesquiterpene lactone Conferone (sesquiterpenoids), have emerged as the core lead compounds with the greatest translational potential in current MDR reverser research, attributed to their potent in vitro and in vivo MDR reversal activity, low toxicity, and excellent druggable modifiability. At the same time, we point out bottlenecks, such as low bioavailability, insufficient in vivo evidence, and unclear structure–activity relationship and put forward a proposal to address these bottlenecks. At the same time, the bottlenecks of low bioavailability, insufficient vivo evidence and unclear structure–activity relationship have been pointed out, and future research directions such as nano-delivery, structural optimization and combination strategies have been proposed to provide theoretical foundations and potential practical pathways for the clinical translation research of terpenoid compounds, whose clinical application still requires further in vivo validation and translational research support.