[Transcriptome analysis of rhizome of Polygonatum cyrtonema and identification of candidate genes involved in biosynthetic pathway of steroidal saponin].

To enrich the transcriptome data in rhizome of Polygonatum cyrtonema seedlings, identify candidate functional genes involved in steroidal saponin biosynthesis and provide genetic resources for the research on anabolism pathway and regulatory mechanism of active components in P. cyrtonema, Illumina platform was applied to perform transcriptomic sequencing of rhizome of P. cyrtonema, followed by a series of bioinformatics analysis on RNA-seq data, including de novo assembly, annotation, classification and metabolic pathway analysis of the assembled unigene. Meanwhile, a deep analysis on the steroidal saponin biosynthesis in secondary metabolism pathway was performed. The results showed a total of 126 546 unigene were obtained by de novo transcriptome assembly, of which 47 226 were annotated. Of these, 16 499 unigene were mapped to 132 specific pathways, of which 2 768 were identified to be involved in 22 secondary metabolic pathways. One hundred and thirteen unigene were identified from the transcriptome database, which encoded 27 metabolic enzymes associated with steroidal saponin biosynthesis and shared similarity with 45 functional genes in Arabidopsis thaliana. In conclusion, a series of candidate functional genes, which might be involved in steroidal saponin biosynthesis, were selected from the transcriptome database of P. cyrtonema rhizome. Further investigation of these candidate genes will provide insight into their actual functions in the steroidal saponin biosynthetic pathway in P. cyrtonema. In addition, this study also provide abunant reference data for transcriptome characterization of P. cyrtonema and has important significance for functional genomics of P. cyrtonema.

Diosgenin intervention: targeting lipophagy to counter high glucose diet-induced lipid accumulation and lifespan reduction.

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 Caenorhabditis elegans 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 C. elegans 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 daf-2, daf-16, skn-1, glp-1, eat-2, let-363, and pha-4. Specifically, DG regulates lipophagy, the autophagy-mediated degradation of lipid droplets, in C. elegans, thereby inhibiting fat accumulation. Furthermore, DG treatment did not alter the triglyceride levels in the fat-6 and fat-7 single mutants and fat-6;fat-7 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. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04017-3.

Anticancer Activity of Diosgenin and Its Molecular Mechanism.

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.

Developments in the Antitumor Activity, Mechanisms of Action, Structural Modifications, and Structure-Activity Relationships of Steroidal Saponins.

Steroidal saponins, a class of natural products formed by the combination of spirosteranes with sugars, are widely distributed in plants and have various biological activities, such as antitumor, anti-inflammatory, anti-bacterial, anti-Alzheimer's, anti-oxidation, etc. Particularly, extensive research on the antitumor property of steroidal saponins has been conducted. Steroidal sapogenins, the aglycones of steroidal saponins, also have attracted much attention due to a vast range of pharmacological activities similar to steroidal saponins. In the past few years, structural modifications on the aglycones and sugar chains of steroidal saponins have been carried out and some achievements have been made. In this mini-review, the antitumor activity, action mechanisms, and structural modifications, along with the structure-activity relationships of steroidal saponins and their derivatives, are summarized.

Anti-inflammatory steroidal sapogenins and a conjugated chalcone-stilbene from Dracaena usambarensis Engl.

Four new steroidal sapogenins, dracaenogenins CF (1-4), a new conjugated chalcone-stilbene, 3''-methoxycochinchinenene H (5) together with eight known compounds namely, (25S)-spirosta-1,4-dien-3-one (6), trans-resveratrol (7), 4,4'-dihydroxy-3'-methoxychalcone (8), N-trans-coumaroyltyramine (9), N-trans-p-coumaroyloctopamine (10), N-trans-feruloyloctopamine (11), 7-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-N2,N3-bis(4-hydroxyphenethyl)-6-methoxy-1,2-dihydronaphthalene-2,3-dicarboxamide (12) and grossamide (13) were isolated from the stems of Dracaena usambarensis Engl. from Kenya. It is important to note that compounds 12 and 13 are being reported from this genus for the first time. Structural elucidation of the isolated compounds was done using spectroscopic (NMR, UV, IR, optical rotation) and spectrometric (HRESIMS) techniques. The absolute and relative configurations of the isolated compounds were determined by employing single crystal X-ray crystallography analysis, NOESY correlations and coupling constants. The anti-inflammatory potencies of the isolated compounds were evaluated by measuring the levels of four cytokines (IL-1ß, IL-2, GM-CSF and TNF-α) in the supernatant media of human peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS). At the tested concentration of 100 µM, the new conjugated chalcone-stilbene 5, the dihydrochalcone, 8 and the lignanamide, 13 were substantially more potent than the standard drug, ibuprofen, inhibiting the release of all the cytokines, IL-1ß, IL-2, GM-CSF and TNF-α from 0.06-58.04% compared to LPS control. These compounds should therefore be considered for development into anti-inflammatory drug candidates. Compound 7 significantly decreased the release of GM-CSF (6.11% of LPS control) and TNF-α (18.35% of LPS control). The cytokine TNF-α was sensitive to all the tested compounds 1-13.

Inclusion complex between ß-cyclodextrin and hecogenin acetate produces superior analgesic effect in animal models for orofacial pain.

Hecogenin acetate (HA) is a steroidal sapogenin-acetylated with pharmacological properties which have already been described in the literature such as, anti-inflammatory, anti-hyperalgesic and antinociceptive, but it has low solubility in aqueous media. Therefore, in an attempt to overcome this, we set out to create inclusion complexes between HA and b-cyclodextrin (b-CD) and evaluate the antinociceptive effects in the orofacial nociception in mice. The complexes were prepared using different methods in the molar ratios 1:1 and 1:2 and characterized physicochemically. The results of the physicochemical characterization elucidated inclusion complexes formation between b-CD and HA by freeze drying method in the molar ratio 1:2, which obtained a complexation efficiency of 92% and produced superior analgesic effect in animal models for orofacial pain at a lower dose when compared to HA alone.