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  • Fenugreeks (Trigonella L. spp.), belonging to the legume family (Fabaceae), are well-known multipurpose crops that their materials are currently received much attention in the pharmaceutical and food industries for the production of healthy and functional foods all over the world. Iran is one of the main diversity origins of this valuable plant. Therefore, the aim of the present study was to explore vitamins, minerals, and fatty acids profile, proximate composition, content of diosgenin, trigonelline, phenolic acids, total carotenoids, saponins, phenols, flavonoids, and tannins, mucilage and bitterness value, and antioxidant activity of the seed of thirty populations belonging to the ten different Iranian Trigonella species.

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  • The aim of this study was to investigate the effects of polyphyllin Ⅶ (PP Ⅶ) on proliferation, apoptosis, and cell cycle of diffuse large B-cell lymphoma (PLBCL) cell lines U2932 and SUDHL-4. The DLBCL cell lines were divided into a control group and a PPⅦ group, and experiments were conducted using MTT assay, flow cytometry, and Western blotting.Results showed that compared with the control group, PPⅦ significantly inhibited the proliferation of U2932 and SUDHL-4 cells (<0.05). Apoptosis assays demonstrated that treatment with 0.50 and 1.00 µmol/L PP Ⅶ significantly increased the apoptosis rates of both cell lines (<0.05), upregulated apoptosis-related proteins, and downregulated Bcl-2 protein level (<0.05). Cell cycle analysis revealed that PPⅦ treatment led to an increase in G0/G1-phase cells (<0.05) and a decrease in G2/M-phase cells (<0.05), significantly downregulated cyclin D1, CDK4, CDK6, and survivin protein expression (<0.05). In conclusion, PPⅦ exerted anti-lymphoma effects by inhibiting proliferation, promoting apoptosis, and inducing G0/G1 phase arrest in DLBCL cells.

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  • Metabolic-associated fatty liver disease (MAFLD) is one of the most common liver diseases worldwide; however, its pathogenesis and treatment methods have not been perfected. NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) is a promising therapeutic target for MAFLD. Diosgenin (DG) is a natural compound that was identified in a traditional Chinese herbal medicine, which has pharmacological effects, such as anti-inflammatory, antioxidant, hepatoprotective, and hypolipidemic activities. In this study, we examined the effects and molecular mechanisms of DG on MAFLD in vitro and in vivo. We established a rat model by administering a high-fat diet (HFD). We also generated an in vitro MAFLD model by treating HepG2 cells with free fatty acids (FFAs). The results indicated that DG attenuated lipid accumulation and liver injury in both in vitro and in vivo models. DG downregulated the expression of NLRP3, apoptosis-associated speckle-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), gasdermin D (GSDMD), GSDMD-n, and interleukin-1β (IL-1β). In addition, we silenced and overexpressed NLRP3 in vitro to determine the effects of DG on antiMAFLD. Silencing NLRP3 enhanced the effect of DG on the treatment of MAFLD, whereas NLRP3 overexpression reversed its beneficial effects. Taken together, the results show that DG has a favorable effect on attenuating MAFLD through the hepatic NLRP3 inflammasome-dependent signaling pathway. DG represents a natural NLRP3 inhibitor for the MAFLD treatment.

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  • Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury-specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research (in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc (AXER-204), fasudil, phosphatase and tensin homolog protein (PTEN) antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide, (-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.

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  • Diosgenin is an important steroidal precursor renowned for its diverse medicinal uses. It is predominantly sourced from Dioscorea species, particularly Dioscorea zingiberensis. Dioscorea zingiberensis has an ability to accumulate 2-16% diosgenin in its rhizomes. In this study, a diverse population of 180 D. zingiberensis accessions was used to evaluate the genomic regions associated with diosgenin biosynthesis by the genome wide association study approach (GWAS).

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  • The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide in recent years, causing severe economic and social burdens. Therefore, the lack of currently approved drugs for anti-NAFLD has gradually gained attention. SIRT1, as a member of the sirtuins family, is now the most widely studied in the pathophysiology of many metabolic diseases, and has great potential for preventing and treating NAFLD. Natural products such as Diosgenin (DG) have the potential to be developed as clinical drugs for the treatment of NAFLD due to their excellent multi-target therapeutic effects. In this study, we found that DG can activate the SIRT1/PGC-1α pathway and upregulate the expression of its downstream targets nuclear respiratory factor 1 (NRF1), complex IV (COX IV), mitofusin-2 (MFN2), and PPARα (perox-isome proliferator-activated receptor α) in SD rats induced by high-fat diet (HFD) and HepG2 cells caused by free fatty acids (FFAs, sodium oleate: sodium palmitate = 2:1). Conversely, the levels of dynamin-related protein 1 (DRP1) and inflammatory factors, including NF-κB p65, IL6, and TNFα, were downregulated both in vitro and in vivo. This improved mitochondrial dysfunction, fatty acid oxidation (FAO), lipid accumulation, steatosis, oxidative stress, and hepatocyte inflammation. Subsequently, we applied SIRT1 inhibitor EX527 and SIRT1 agonist SRT1720 to confirm further the necessity of activating SIRT1 for DG to exert therapeutic effects on NAFLD. In summary, these results further demonstrate the potential therapeutic role of DG as a SIRT1 natural agonist for NAFLD. (Graphical Abstracts).

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  • Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG-HA and DSPE-PEG-TK-PEG, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration.

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  • Saponins are bioactive components of many medicinal plants, possessing complicated chemical structures and extensive pharmacological activities, but the production of high-value saponins remains challenging. In this study, a 6'-O-glucosyltransferase PpUGT7 (PpUGT91AH7) was functionally characterized from Paris polyphylla Smith var. yunnanensis (Franch.) Hand. -Mazz., which can transfer a glucosyl group to the C-6' position of diosgenin-3-O-rhamnosyl-(1 → 2)-glucoside (1), pennogenin-3-O-rhamnosyl-(1 → 2)-glucoside (2), and diosgenin-3-O-glucoside (5). The K and K values of PpUGT7 towards the substrate 2 were 8.4 μM and 2 × 10 s, respectively. Through molecular docking and site-directed mutagenesis, eight residues were identified to interact with the sugar acceptor 2 and be crucial for enzyme activity. Moreover, four rare ophiopogonins and ginsenosides were obtained by combinatorial biosynthesis, including an undescribed compound ruscogenin-3-O-glucosyl-(1 → 6)-glucoside (10). Firstly, two monoglycosides 9 and 11 were generated using a known sterol 3-O-β-glucosyltransferase PpUGT80A40 with ruscogenin (7) and 20(S)-protopanaxadiol (8) as substrates, which were further glycosylated to the corresponding diglycosides 10 and 12 under the catalysis of PpUGT7. In addition, compounds 7-11 were found to show inhibitory effects on the secretion of TNF-α and IL-6 in macrophages RAW264.7. The findings provide valuable insights into the enzymatic glycosylation processes in the biosynthesis of bioactive saponins in P. polyphylla var. yunnanensis, and also serve as a reference for utilizing UDP-glycosyltransferases to construct high-value or rare saponins for development of new therapeutic agents.

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  • Diosgenin (DG), a well-known steroidal sapogenin, is abundantly found in the plants of the Dioscoreaceae family and exhibits diverse pharmacological properties. In our previous study, we demonstrated that DG supplementation protected from high glucose-induced lipid deposition, oxidative damage, and lifespan reduction. Nevertheless, the precise biological mechanisms underlying the beneficial effects of DG have not yet been described. In this context, the present study aims to elucidate how DG reduces molecular and cellular declines induced by high glucose, using the powerful genetics of the model. Treatment with DG significantly (p < 0.01) prevented fat accumulation and extended lifespan under high-glucose conditions without affecting physiological functions. DG-induced lifespan extension was found to rely on longevity genes , , , , , , and . Specifically, DG regulates lipophagy, the autophagy-mediated degradation of lipid droplets, in thereby inhibiting fat accumulation. Furthermore, DG treatment did not alter the triglyceride levels in the and single mutants and ; double mutants, indicating the significant role of stearoyl-CoA desaturase genes in mediating the reduction of fat deposition by DG. Our results provide new insight into the fat-reducing mechanisms of DG, which might develop into a multitarget drug for preventing obesity and associated health complications; however, preclinical studies are required to investigate the effect of DG on higher models.

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  • Wall. ex Griseb. is an endangered species of the Dioscoreaceae family. It is the most commonly consumed wild species as a vegetable due to its high protein, vital amino acid, vitamin, and mineral content. There are approximately 613 species in the genus Plum. ex L., which is found in temperate and tropical climates. , a plant species widespread across tropical and sub-tropical regions, called by different names in different languages. In English, it is commonly referred to as "Wild yam" or "Elephant foot". The Sanskrit name for this plant is "Varahikand," while in Hindi, it is known as "Gun" or "Singly-mingly." The Urdu language refers to it as "Qanis," and in Nepali, it is called "Tarul," "Bhyakur," or "Ghunar." has been used to cure a wide range of human ailments for centuries. This plant has nutritional and therapeutic uses and also contains high amounts of steroidal saponins, allantoin, polyphenols, and most notably, polysaccharides and diosgenin. These bioactive chemicals have shown potential in providing protection against a wide spectrum of inflammatory conditions, including enteritis (inflammation of the intestines), arthritis (joint inflammation), dermatitis (skin inflammation), acute pancreatitis (inflammation of the pancreas), and neuro inflammation (inflammation in the nervous system). Furthermore, the valuable bioactive chemicals found in have been associated with a range of beneficial biological activities, such as antibacterial, antioxidant, anti-inflammatory, immunomodulatory, hepatoprotective, and cytotoxic properties. Sapogenin steroidal chemicals are highly valued in the fields of medicine, manufacturing, and commerce. It has both expectorant and sedative properties. It is employed in the treatment of cardiovascular diseases, encompassing various ailments related to the heart and blood vessels, skin disease, cancer, immune deficiencies, and autoimmune diseases. Additionally, it finds application in managing disorders of the central nervous system and dysfunctional changes in the female reproductive system. Furthermore, it is valued for its role in treating bone and joint diseases. Metabolic disorders are also among the ailments for which is employed. It has traditionally been used as a vermifuge, fish poison, and to kill lice. Diosgenin, a steroidal compound found in , plays a crucial role as a precursor in the chemical synthesis of various hormones. Due to the presence of valuable bioactive molecule, like corticosterone and sigmasterol, is cultivated specifically for the extraction of these beneficial phytochemicals. The current study aims to assess medicinal properties, ethnobotanical usage, phytochemicals, pharmacological properties, threats, and conservation techniques.

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