Lysimachia capillipes Hemsl. saponins ameliorate colorectal cancer in mice via regulating gut microbiota and restoring metabolic profiles.

Lysimachia capillipes Hemsl., a traditional Chinese medicine (TCM), is commonly prescribed for its anti-inflammatory and anti-tumor properties. Pharmacological studies have demonstrated that Lysimachia capillipes Hemsl. saponins (LCS) are the primary bioactive component. However, its mechanism for treating colorectal cancer (CRC) is still unknown. Increasing evidence suggests a close relationship between CRC, intestinal flora, and host metabolism. Thus, this study aims to investigate the mechanism of LCS amelioration of CRC from the perspective of the gut microbiome and metabolome. As a result, seven gut microbiotas and fourteen plasma metabolites were significantly altered between the control and model groups. Among them, one gut microbiota genera (Monoglobus) and six metabolites (Ureidopropionic acid, Cytosine, L-Proline, 3-hydroxyanthranilic acid, Cyclic AMP and Suberic acid) showed the most pronounced callback trend after LCS administration. Subsequently, the correlation analysis revealed significant associations between 68 pairs of associated metabolites and gut microbes, with 13 pairs of strongly associated metabolites regulated by the LCS. Taken together, these findings indicate that the amelioration of CRC by LCS is connected to the regulation of intestinal flora and the recasting of metabolic abnormalities. These insights highlight the potential of LCS as a candidate drug for the treatment of CRC.

Exploring Steroidal Saponin Composition and Morphometric Characteristics of Rhizomes from Trillium govanianum Wall. ex D. Don: Inference for Medicinal Properties and Genetic Stock Improvement.

Trillium govanianum, a medicinal herb, exhibiting diverse morphometric traits and phytochemicals across developmental stages of plants. The changes in the chemical profile and steroidal saponin levels in the rhizome of T. govanianum across different developmental stages were previously unknown. This study categorizes rhizomes into three types based on scar presence: juvenile (5-10 scars, Type I), young (11-19 scars, Type II), and mature (21-29 scars, Type III). Rhizomes show varying sizes (length 1.2-4.7 cm, girth 0.3-1.6 cm), weight (0.18-5.0 g), and extractive yields (9.7-16.1 % w w-1), with notable differences in saponin content (5.95-21.9 mg g-1). Ultra-high performance liquid chromatography-MS/MS (UHPLC-QTOF-MS/MS)-based chemical profiling identifies 31 phytochemicals, mainly including diverse saponins. Ultra-high performance liquid chromatography coupled with evaporative light scattering detection (UHPLC-ELSD)-based quantitative analysis of seven key saponins reveals stage-specific accumulation patterns, with protodioscin (P) and dioscin (DS) predominant in mature rhizomes. Statistical analysis confirms significant variation (p=0.001) in saponin levels across developmental stages with chemical constituent protodioscin (P=4.03±0.03-15.76±0.14 mg g-1, PAve=9.79±3.03 mg g-1) and dioscin (DS=1.23±0.06-3.93±0.07 mg g-1, DSAve=2.59±0.70 mg g-1), with acceptable power (p=0.738; |δ|>0.5) statistics for effective sample size (n=27 samples used in the study) of T. govanianum. Principal Component Analysis (PCA) and Euclidean clustering further highlighted chemotype distinctions.

Two previously undescribed cholestanol saponins from the rhizomes of Paris fargesii var. petiolata.

Two previously undescribed cholestanol saponins, parpetiosides F - G (1-2), and six known analogs (3-8) were isolated from the rhizomes of Paris fargesii var. petiolata. Their structures were elucidated by extensive spectroscopic data analysis and chemical methods. Compound 1 was a rare 6/6/6/5/5 fused-rings cholestanol saponin with disaccharide moiety linked at C-26 of aglycone which was hardly seen in genus Paris. All of these compounds were discovered in this plant for the first time. In addition, the cytotoxicities of saponins (1-8) against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated by CCK-8 method, and saponins 5-8 displayed certain cytotoxicities. The strong interactions between saponins 5-8 and SCUBE3, an oncogene for glioma cells, were displayed by molecular docking.

Chemometric guided isolation of new triterpenoid saponins as acetylcholinesterase inhibitors from seeds of Achyranthes bidentata Blume.

Achyranthes bidentata Blume (Amaranthaceae) is an annual or perennial herb widely used as ethnomedicine in Traditional Chinese Medicine for treating fever, cold, ulcers, mensural pain, dementia, and osteoporosis. In the current study, UPLC-IM-Q-TOF-MS/MS-based chemometric approach was adopted for the tentative identification of fifty-six compounds in the extract and fractions of A.bidentata seeds. Further, the chemometric-guided isolation led to the isolation of two previously undescribed oleanane-type triterpenoid saponins, named achyranosides A-B (27 and 30), along with three known compounds (31, 44, and 23) from water fraction of A. bidentata seeds. The structures of new compounds were elucidated based on the detailed analysis of NMR, HR-ESI-MS, FT-IR spectral data, and GC-FID techniques. The isolated compounds in vitro acetylcholinesterase inhibitory activity revealed the promising activity of chikusetsusaponin IVa (23) (IC50 = 63.7 µM) with mixed type of AChE inhibition in enzyme kinetic studies. Additionally, in silico binding free energy of isolated compounds disclosed the greater stability of enzyme-ligand complex owing to underlying multiple H-bond interactions. Overall, the study demonstrates the effectiveness of a chemometric-guided approach for the phytochemical exploration and isolation of new oleanane-type triterpenoid saponins from A. bidentata seeds.

Saponins and flavonoids from Bacopa floribunda plant extract exhibit antioxidant and anti-inflammatory effects on amyloid beta 1-42-induced Alzheimer's disease in BALB/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa floribunda (BF), a locally available plant has been employed traditionally as memory enhancer in Southwestern, Nigeria. It has been utilized in traditional and Ayurvedic medicine as brain tonic for enhancing memory, anti-aging and forestalling series of psychological disorders. However, there is a dearth of scientific information on the mechanism(s) of action of important phytochemicals from BF extract on dementia. AIM OF THE STUDY: Alzheimer's disease, the commonest form of dementia has been postulated to triple by 2050 as a result of increase in life expectancy. This study therefore assessed and compared the possible mechanism(s) of action of flavonoids and saponins from BF on Amyloid beta (Aß1-42)-induced dementia in male BALB/c mice. MATERIALS AND METHODS: Eighty (80) healthy BALB/c mice divided into 10 groups (n = 8) were given a single bilateral ICV injection of Aß1-42 or normal saline. Graded doses of Saponins and flavonoids (50, 100 and 200 mg/kg) were used as treatment for 21 days. Hippocampal homogenates were assayed for the levels of antioxidants, oxidative stress and neuroinflammatory markers. In vitro antioxidant activity of flavonoids and saponins were equally assessed using standard procedures. The extent of microglial activation was quantified through immunohistochemistry procedure. RESULTS: Aß1-42 successfully caused a spike in hippocampal levels of MDA, IL1ß, TNF-α including MPO levels and invariably decreased antioxidant activities. Likewise an increase in reactive microglia (microgliosis) was observed. However, crude saponins and flavonoids from BF were able to suppress microgliosis, oxidative stress and neuroinflammation induced by Aß1- 42 and were observed to be more effective at higher doses of saponins (100 mg/kg and 200 mg/kg) and flavonoid (100 mg/kg). CONCLUSIONS: Phytochemicals from BF efficiently exhibited dose dependent alleviation of some symptoms associated with Alzheimer's disease.

Ultrasound-Assisted Extraction of Total Saponins from Aralia taibaiensis: Process Optimization, Phytochemical Characterization, and Mechanism of α-Glucosidase Inhibition.

PURPOSE: Aralia taibaiensis, a medicinal food plant, and total saponins from its root bark extract inhibit α-glucosidase activity, which is associated with type 2 diabetes; however, the inhibitory mechanism is unknown. Furthermore, a green extraction technique superior to conventional hot reflux extraction (HRE) is needed for the rapid and easy extraction of A. taibaiensis total saponins (TSAT) to exploit and utilize this resource. Our aim was to develop a green extraction method for obtaining TSAT and to investigate the mechanism by which TSAT inhibits α-glucosidase. MATERIALS AND METHODS: In this study, the ultrasound-assisted extraction (UAE) process was optimized using a Box-Behnken design, and the extraction mechanism was investigated using scanning electron microscopy (SEM). High-performance liquid chromatography (HPLC) was used for qualitative and quantitative analyses of TSAT. In vitro glycosylation assays, enzyme kinetics, fluorescence spectroscopy measurements, atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR) and molecular docking techniques were used to investigate the mechanism by which the A. taibaiensis active ingredients inhibit α-glucosidase. RESULTS: The optimal parameters for the extraction yield were obtained as an ethanol concentration of 73%, ultrasound time of 34 min, ultrasound temperature of 61 °C and solid-liquid ratio of 16 g/mL, which were better than HRE. The SEM analysis showed that UAE effectively disrupted plant cells, thus increasing the TSAT yield. In vitro α-glucosidase inhibition experiments showed that both TSAT and its active ingredient, araloside A, inhibited α-glucosidase activity by binding to α-glucosidase, thereby changing the conformation and microenvironment of α-glucosidase to subsequently inhibit enzyme activity. CONCLUSION: The optimal extraction conditions identified here established a basis for future scale-up of ultrasound extraction parameters with the potential for obtaining maximum yields. In vitro enzyme inhibition experiments investigated the mechanism of the TSAT interaction with α-glucosidase and further explored whether araloside A may be the main contributor to the good inhibition of α-glucosidase activity by TSAT.

Total extract of Anemarrhenae Rhizoma attenuates bleomycin-induced pulmonary fibrosis in rats.

Pulmonary fibrosis is a progressive interstitial lung disease with poor prognosis. Anemarrhenae Rhizoma is a traditional Chinese herbal medicine and has been applied in clinical practice for a long history. Recently, components of Anemarrhenae Rhizoma were reported to possess anti-inflammatory and immunomodulatory features; however, the effect of them on pulmonary fibrosis remains unknown. In this study, we explored the therapeutic effect of total extract of Anemarrhenae Rhizoma (TEAR) on bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis rat model was established by a single intratracheal instillation of bleomycin, three doses of TEAR were intragastrically administered for consecutive 28 days. Subsequent to sacrificing of rats, pulmonary fibrosis was observed in rats treated with bleomycin, but administration of TEAR attenuated lung fibrosis, as evidenced by the improved lung histopathological damage and decreased weight loss and lung index. Moreover, TEAR treatment inhibited the inflammatory response in lung fibrosis, which was shown by the reduced nitrogen oxide level and myeloperoxidase activity. Furthermore, TEAR modulated the redox balance in lung tissue by alleviated lipid peroxidation and enhanced enzymatic antioxidants activity. Meanwhile, TEAR protected the rats from fibrosis in a dose-dependent manner, and the anti-fibrotic activity of TEAR may be related to the modulation of TGF-ß1/Smad signaling pathway. Collectively, TEAR alleviates bleomycin-induced pulmonary fibrosis, indicating perspectives for development of a potential agent for lung fibrosis therapy.

A new discovery: Total Bupleurum saponin extracts can inhibit the proliferation and induce apoptosis of colon cancer cells by regulating the PI3K/Akt/mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleurum chinense DC has a history of using herb in China for more than 2000 years, which can be traced back to the Classic of Shennong Materia Medica in the Han Dynasty. Although Saikosaponin, the main active ingredient of Bupleurum, has the effects of anti-tumor, yet we still do not know the mechanism by total Bupleurum saponin extracts (TBSE) produces this effect on colon cancer. AIM OF THE STUDY: It is predicted by network pharmacology that TBSE may play an anti-colon cancer role by regulating the PI3K-Akt-mTOR pathway. The purpose of this study is to investigate whether TBSE inhibits proliferation and promote apoptosis of colon cancer cells by regulating PI3K/Akt/mTOR pathway. MATERIALS AND METHODS: The effect of saikosaponins on the proliferation of SW480 and SW620 cells was detected by CCK-8, apoptosis was determined by flow cytometry, morphological changes of cells were observed by microscope, nuclear morphological changes were observed after immunofluorescence staining, the expression of apoptosis-related proteins Bax, Bcl2, Caspase3, Caspase9, Cleaved Caspase3 and Cleaved Caspase9 were detected by Western Blot, and the expression of apoptosis-related genes Bax, Bcl2, Caspase3 and Caspase9 were detected by RT-PCR. According to the theory of network pharmacology, the potential targets of saikosaponins and colon cancer were predicted by database Pharmmapper and Genecards database respectively. The intersection of saikosaponins and colon cancer was enriched and analyzed on the Metascape platform. Then, the expression of PI3K/Akt/mTOR pathway related protein PI3K, Akt, Mtor, p-PI3K, p-Akt, p-mTOR were detected by Western Blot, and the corresponding amount of RNA expressions in the pathway was confirmed by RT-PCR. RESULTS: The results of CCK-8 demonstrated that the survival rate of SW480 and SW620 cells decreased significantly when the concentration of TBSE was in the range of 25-200 µg/ml. The morphological observation showed that the cells lost normal cell morphology, cytoplasmic condensation, and partial loss of adhesion after treatment with TBSE. Flow cytometry indicated that the apoptosis rates of SW480 cells and SW620 cells treated with TBSE (50 µg/ml) were 48.47% ± 1.20% and 36.13% ± 1.76%, respectively. Western Blot firstly confirmed that TBSE significantly up-regulated the expression of pro-apoptotic proteins Bax, Caspase3, Caspase9, Cleaved Caspase3 and Cleaved Caspase9, and down-regulated the expression of anti-apoptotic protein Bcl2. And RT-PCR results implied that TBSE significantly up-regulated the gene expression of apoptotic factors Bax, Caspase3 and Caspase9, and significantly decreased the gene expression of Bcl2. It was predicted that the PI3K/Akt/mTOR pathway may be the main regulatory object of the antitumor effect of TBSE by network pharmacology. Subsequent WB experiment also revealed that TBSE could significantly down-regulate (P < 0.01) the expressions of PI3K, Akt, mTOR and phosphorylated proteins P-PI3K, P-Akt, P-MTOR. Meanwhile, RT-PCR results also indicated that TBSE could significantly down-regulate (P < 0.01) the gene expression levels of PI3K, Akt and mTOR. CONCLUSIONS: TBSE activated Bax/Bcl2 and caspase-9/caspase-3 cascade to induced apoptosis of human colon cancer SW480 and SW60 cells in a dose-dependent manner, which was obviously related to the inhibition of PI3K/Akt/mTOR signaling pathway.

The anti-tumor effect of OP-B on ovarian cancer in vitro and in vivo, and its mechanism: An investigation using network pharmacology-based analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Maidong (Liliaceae) is used as a yin-nourishing medication for the treatment of cardiovascular disease, inflammation, and assistant cancer chemotherapy in the clinic. Ophiopogonin B (OP-B), a major saponin extracted from Maidong, is reported to have potential antitumor activities against various human cancers. However, the effects of OP-B on human ovarian cancer (OC) and the potential mechanisms of action are yet elusive. AIM OF THE STUDY: In this study, we aimed to explore the potential molecular mechanisms of OP-B in the treatment of OC using network pharmacology. In vivo and in vitro experiments were conducted to further verify the therapeutic effects of OP-B on OC. MATERIALS AND METHODS: To investigate the functions of OP-B against OC holistically, the related targets of OP-B and OC were each predicted based on four public databases. Subsequently, the identified PPI network was constructed to detect the hub potential targets. In addition, GO and KEGG enrichment analysis were applied by Metascape database. Furthermore, we simultaneously investigated the anticancer effects of OP-B on SKOV3 and A2780 human ovarian cancer cells using a cell viability assay, transwell assay, and an image-based cytometric assay. The quantitative real-time PCR and western-blot assay were used to validate the RNA and protein levels of target genes in OP-B treated OC cells. At last, SKOV3-bearing BALB/c nude mice were applied to observe the effectiveness and toxicity of OP-B. RESULTS: Through network pharmacological analysis, OP-B was found to play a critical role in OC via multiple targets and pathways, especially the STAT3 signaling pathways. In addition, in vitro experiments found OP-B suppressed SKOV3 and A2780 cells proliferation in a time and concentration dependent manner, and markedly impaired cancer cell migration. Flow cytometry analysis revealed that OP-B significantly increased early and late apoptosis, induced G2/M phase cell cycle arrest in SKOV3 cells and G0/G1 phase cell cycle arrest in A2780 cells. Moreover, OP-B administration down-regulated the expression of p-STAT3 protein, whereas the RNA expression and total protein levels of STAT3 were not altered. Finally, in vivo experiments confirmed the therapeutic effects of OP-B on OC in nude mice with low toxicity in heart, liver, lung, and kidney. CONCLUSION: OP-B could efficiently suppress OC cellular proliferation, migration and induce apoptosis, cell cycle arrest mainly via the regulation of STAT3 signaling pathway. This study provides a promising potential application for an alternative to chemotherapy in ovarian cancer.

Saponins from Nigella glandulifera seeds attenuate collagen-induced rheumatoid arthritis in rats via the OPG/RANKL/NF-κB and Ang/Tie-2 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Nigella glandulifera Freyn et Sint. (N. glandulifera) seeds are widely used in traditional Uyghur medicine for a variety of immuno-inflammatory diseases. The total saponins from N. glandulifera seeds (TSNGS) have been shown to have analgesic, antioxidant, and anti-inflammatory effects that can alleviate joint pain and swelling. AIM OF THE STUDY: Rheumatoid arthritis (RA) is a chronic and progressive, debilitating autoimmune disease for which current treatments are not sufficiently effective and result in unsatisfactory side effects. This study aimed to mechanistically investigate the therapeutic effects of TSNGS on RA. MATERIALS AND METHODS: Qualitative analysis of TSNGS was performed using ultra-high-performance liquid chromatography-Q-Orbitrap-high-resolution mass spectrometry. Rats with collagen-induced arthritis (CIA), IL-1ß-induced HFLS-RAs, and VEGF-induced HUVECs were analyzed to determine the efficacy and mechanism of TSNGS on RA. RESULTS: Twenty-one compounds were identified in TSNGS. TSNGS (10, 50, or 250 mg/kg) reduced the severity of arthritis, indicated by a lower arthritis score, reduced paw swelling, and body weight in rats with CIA. TSNGS ameliorated histopathological changes involving inflammatory infiltration, bone degeneration, and angiogenesis in knee and ankle joints. TSNGS improved the immuno-inflammatory response by restoring the levels of the cytokines IFN-γ, TNF-α, IL-1ß, IL-6, IL-17A, IL-4, and IL-10, and increasing the number of CD4+CD25+ Tregs in the peripheral circulation and Foxp3 levels in knee joints in rats with CIA. Furthermore, TSNGS increased the OPG/RANKL ratio and downregulated p-p65 in serum and joint synovia. Inhibition of angiogenesis by TSNGS was associated with recovery of the angiogenesis-related Ang/Tie-2 signaling pathway. CONCLUSIONS: It was established that TSNGS provides a therapeutic effect on RA by alleviating synovitis, bone degeneration, and angiogenesis via the OPG/RANKL/NF-κB and Ang/Tie-2 pathways and may be used for the treatment of RA.

Terrestrosin D, a spirostanol saponin from Tribulus terrestris L. with potential hepatorenal toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Tribuli (FT) has been commonly used as a traditional medicine for thousands of years. With the diverse uses of FT, more attention has been paid to its hepatorenal toxicity. However, the compounds causing the hepatorenal toxicity of FT remain undetermined. Terrestrosin D (TED), a major spirostanol saponin isolated from FT, may exert hepatorenal toxicity. AIM OF THE STUDY: This study aimed to evaluate the potential hepatorenal toxicity of TED, and preliminarily explore the possible mechanism of TED-induced hepatorenal toxicity. MATERIALS AND METHODS: Cytotoxicity assays, a repeated-dose 28-day in-vivo study, a toxicokinetic study, and a tissue distribution study were used to evaluate the potential hepatorenal toxicity of TED. Furthermore, network pharmacology was applied to preliminarily explore the possible mechanism of TED-induced hepatorenal toxicity. RESULTS: Both the in vitro and in vivo studies showed that the spirostanol saponin TED had potential hepatorenal toxicity. Nonetheless, hepatorenal toxicity induced by oral treatment with TED at a dosage range of 5 - 15 mg/kg daily for 28 consecutive days to Sprague-Dawley (SD) rats was reversible after 14 days of TED withdrawal. The toxicokinetic study demonstrated that the systematic exposure of SD rats to TED had an accumulation phenomenon and a dose-dependent trend after a 28-day repeated-dose oral administration. The tissue distribution study revealed that TED had a targeted distribution in the liver and kidneys accompanied by a phenomenon of accumulation in SD rats. Network pharmacology combined with molecular docking methods was used to screen for the key targets (HSP90AA1, CNR1, and DRD2) and the key pathways of TED-induced hepatorenal toxicity. CONCLUSIONS: The spirostanol saponin TED, a major spirostanol saponin isolated from FT, had potential hepatorenal toxicity.

Triterpenoid Saponins from the Cultivar "Green Elf" of Pittosporum tenuifolium.

Four oleanane-type glycosides were isolated from a horticultural cultivar "Green Elf" of the endemic Pittosporum tenuifolium (Pittosporaceae) from New Zealand: three acylated barringtogenol C glycosides from the leaves, with two previously undescribed 3-O-ß-d-glucopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C, 3-O-ß-d-galactopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C, and the known 3-O-ß-d-glucopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C (Eryngioside L). From the roots, the known 3-O-ß-d-glucopyranosyl-(1→2)-ß-d-galactopyranosyl-(1→2)-ß-d-glucuronopyranosyloleanolic acid (Sandrosaponin X) was identified. Their structures were elucidated by spectroscopic methods including 1D- and 2D-NMR experiments and mass spectrometry (ESI-MS). According to their structural similarities with gymnemic acids, the inhibitory activities on the sweet taste TAS1R2/TAS1R3 receptor of an aqueous ethanolic extract of the leaves and roots, a crude saponin mixture, 3-O-ß-d-glucopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-ß-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C, and Eryngioside L were evaluated.

New Steroidal Saponins Isolated from the Rhizomes of Paris mairei.

The genus Paris is an excellent source of steroidal saponins that exhibit various bioactivities. Paris mairei is a unique species and has been widely used as folk medicine in Southwest China for a long time. With the help of chemical methods and modern spectra analysis, five new steroidal saponins, pamaiosides A-E (1-5), along with five known steroidal saponins 6-10, were isolated from the rhizomes of Paris mairei. The cytotoxicity of all the new saponins was evaluated against human pancreatic adenocarcinoma PANC-1 and BxPC3 cell lines.

Spirostanol Saponins from Flowers of Allium Porrum and Related Compounds Indicating Cytotoxic Activity and Affecting Nitric Oxide Production Inhibitory Effect in Peritoneal Macrophages.

Saponins, a diverse group of natural compounds, offer an interesting pool of derivatives with biomedical application. In this study, three structurally related spirostanol saponins were isolated and identified from the leek flowers of Allium porrum L. (garden leek). Two of them were identical with the already known leek plant constituents: aginoside (1) and 6-deoxyaginoside (2). The third one was identified as new component of A. porrum; however, it was found identical with yayoisaponin A (3) obtained earlier from a mutant of elephant garlic Allium ampeloprasun L. It is a derivative of the aginoside (1) with additional glucose in its glycosidic chain, identified by MS and NMR analysis as (2α, 3ß, 6ß, 25R)-2,6-dihydroxyspirostan-3-yl ß-D-glucopyranosyl-(1 → 3)-ß-D-glucopranosyl-(1 → 2)-[ß-D-xylopyranosyl-(1 → 3)]-ß-D-glucopyranosyl]-(1 → 4)-ß-D-galactopyranoside, previously reported also under the name alliporin. The leek native saponins were tested together with other known and structurally related saponins (tomatonin and digitonin) and with their related aglycones (agigenin and diosgenin) for in vitro cytotoxicity and for effects on NO production in mouse peritoneal cells. The highest inhibitory effects were exhibited by 6-deoxyaginoside. The obtained toxicity data, however, closely correlated with the suppression of NO production. Therefore, an unambiguous linking of obtained bioactivities of saponins with their expected immunobiological properties remained uncertain.

Saikosaponin D: review on the antitumour effects, toxicity and pharmacokinetics.

CONTEXT: Bupleuri Radix, the dried root of Bupleurum chinense DC and Bupleurum scorzonerifolium Willd (Apiaceae), is an important medicinal herb widely used to treat cancers for hundreds of years in Asian countries. As the most antitumour component but also the main toxic component in Bupleuri Radix, saikosaponin D (SSD) has attracted extensive attention. However, no summary studies have been reported on the antitumour effects, toxicity and pharmacokinetics of this potential natural anticancer substance. OBJECTIVE: To analyse and summarise the existing findings regarding to the antitumour effects, toxicity and pharmacokinetics of SSD. MATERIALS AND METHODS: We collected relevant information published before April 2021 by conducting a search of literature available in various online databases including PubMed, Science Direct, CNKI, Wanfang database and the Chinese Biological Medicine Database. Bupleurum, Bupleuri Radix, saikosaponin, saikosaponin D, tumour, toxicity, and pharmacokinetics were used as the keywords. RESULTS: The antitumour effects of SSD were multi-targeted and can be realised through various mechanisms, including inhibition of proliferation, invasion, metastasis and angiogenesis, as well as induction of cell apoptosis, autophagy, and differentiation. The toxicological effects of SSD mainly included hepatotoxicity, neurotoxicity, haemolysis and cardiotoxicity. Pharmacokinetic studies demonstrated that SSD had the potential to alter the pharmacokinetics of some drugs for its influence on CYPs and P-gp, and the oral bioavailability and actual pharmacodynamic substances in vivo of SSD are still controversial. CONCLUSIONS: SSD is a potentially effective and relatively safe natural antitumour substance, but more research is needed, especially in vivo antitumour effects and pharmacokinetics of the compound.

Triterpenoid saponins from the leaves and stems of Pericampylus glaucus and their insulin mimetic activities.

During an attempt to discover insulin mimetics, thirteen new triterpenoid saponins (1-13), including three phytolaccagenic acids (1, 2, and 12) and ten serjanic acids (3-11 and 13), as aglycones were isolated from a 70% ethanol extract of leaves and stems from Pericampylus glaucus. The chemical structures of compounds 1-13 were determined through spectroscopic data analysis, including NMR, IR, and HRESIMS. All isolated compounds (1-13) were evaluated using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a fluorescent-tagged glucose probe to determine their stimulatory effects on glucose uptake in differentiated 3 T3-L1 adipocyte cells. Consequently, four compounds (4, 7, 11, and 12) exhibited stimulatory effects on glucose uptake.

Progress in the Medicinal Value, Bioactive Compounds, and Pharmacological Activities of Gynostemma pentaphyllum.

Gynostemma pentaphyllum (Thunb.) Makino (GP), also named Jiaogulan in Chinese, was known to people for its function in both health care and disease treatment. Initially and traditionally, GP was a kind of tea consumed by people for its pleasant taste and weight loss efficacy. With the passing of the centuries, GP became well known as more than just a tea. Until now, numbers of bioactive compounds, including saponins (also named gypenosides, GPS), polysaccharides (GPP), flavonoids, and phytosterols were isolated and identified in GP, which implied the great medicinal worth of this unusual tea. Both in vivo and in vitro tests, ranging from different cell lines to animals, indicated that GP possessed various biological activities including anti-cancer, anti-atherogenic, anti-dementia, and anti-Parkinson's diseases, and it also had lipid-regulating effects as well as neuroprotection, hepatoprotective, and hypoglycemic properties. With the further development and utilization of GP, the research on the chemical constituents and pharmacological properties of GP were deepening day by day and had made great progress. In this review, the recent research progress in the bioactive compounds, especially gypenosides, and the pharmacological activities of GP were summarized, which will be quite useful for practical applications of GP in the treatment of human diseases.

Psidium guajava leaf extract improves gastrointestinal functions in rats and rabbits: an implication for ulcer and diarrhoea management.

PURPOSE: Psidium guajava L. (Family, Myrtaceae) is reportedly used in ethnomedicine for the treatment of diarrhoea, inflammation, and gastroenteritis. OBJECTIVE: This study evaluated the gastrointestinal function of Psidium guajava leaf extract (PGLE) in rats and rabbits. MATERIALS AND METHODS: Crude ethanolic PGLE was subjected to phytochemical and toxicity tests (acute and sub-acute). Standard analytical procedures were employed to evaluate the in vivo gastrointestinal motility, and gastroprotective effect of PGLE against aspirin-induced ulcers. RESULTS: In the phytochemical analysis, phenols were the highest (48.32 mg) followed by flavonoids (32.74 mg) and least in tannins (7.31 mg). The acute toxicity of PGLE was >6000 mg/kg. Administration of PGLE decreased significantly (p < 0.05) the body weight, while the liver biomarkers were not significantly altered (p > 0.05) when compared to the control. PGLE significantly increased extractible mucus weight and lowered gastric acid secretion in rats (p < 0.05). PGLE decreased significantly (p < 0.05) ulcer scores and indexes, and increased percentage ulcer inhibition in a dose-dependent manner compared to the negative and omeprazole-treated groups. PGLE dose-dependently inhibited basal amplitudes of contractions, and significantly inhibited acetylcholine-induced contractions, terminating them completely at higher doses. CONCLUSION: PGLE may be a good anti-ulcer and anti-diarrhoeal agent, raising the prospect of novel drug development for such applications.

Flavonoids and saponins from Passiflora edulis f. edulis leaves (purple passion fruit) and its potential anti-inflammatory activity.

OBJECTIVES: The objective of this work was to evaluate the anti-inflammatory activity of the aqueous extract, fractions and major compounds, which are isolated and identified from Passiflora edulis f. edulis (purple passion fruit) leaves extract. METHODS: For the isolation of the major compounds, reversed-phase chromatography and normal phase countercurrent chromatography were used. The separation was followed by thin layer chromatography and HPLC-DAD-ELSD. One-dimensional and two-dimensional NMR and ESI-TOF-MS/MS were used for structural elucidation. The anti-inflammatory activity was evaluated on a TPA multiple dose model of skin chronic inflammation in mice. Additionally, myeloperoxidase (MPO) and nitric oxide synthase (NOS) activity assays were performed as possible mechanisms of action studies. KEY FINDINGS AND CONCLUSIONS: The study of the butanolic fraction mainly showed the presence of saponins and flavonoids. Three minor flavonoids were detected; and three known saponins, cyclopassiflosides IX, XI and III were isolated and identified. This is the first unequivocal report of the presence of these compounds in P. edulis f. edulis leaves. The most favourable results of anti-inflammatory activity were obtained for the flavonoid-rich fraction. All the fractions and isolated compounds evaluated, presented high percentages of inhibition of nitric oxide synthase activity.

Panax notoginseng saponins reduces the cisplatin-induced acute renal injury by increasing HIF-1α/BNIP3 to inhibit mitochondrial apoptosis pathway.

Cisplatin (CDDP) may induce apoptosis of renal tubular epithelial cells (RTEC) and cause CDDP-induced acute kidney injury (CAKI) during cancer treatment, but yet lack of preventive measures and effective treatment. As a new Chinese herbal preparation, Panax notoginseng saponins (PNS) has been found to mitigate CDDP-induced CAKI through elevating the expression of HIF-1α in the rat model, according to the data from our previous works. However, the underlying link between HIF-1α and apoptosis has not been well elucidated. The current study as a follow-up work, was aimed to reveal if PNS improves CAKI through HIF-1α-dependent apoptosis. A stably HIF-1α-knockdown human proximal tubular epithelial cell (HK-2) line was established by transfecting a HIF-1α-siRNA into HK-2 cells. Cell viability, mitochondrial function, cell apoptosis ratio and the expression of apoptosis-associated proteins (Cyt C, Bcl2, Bax, caspases 3) were determined. In order to elucidate the underlying mechanism, the expression of HIF-1α and BNIP3 were assessed. Our results showed that treatment of PNS rescued the cell viability of CDDP-injured HK-2 or HIF-1α-knockdown HK-2 cells, and increased the expression levels of ATP and MMP in HK-2 or HIF-1α-knockdown HK-2 cells which were reduced by CDDP. Moreover, PNS treatment decreased the CDDP or CDDP plus HIF-1α-knockdown-induced elevation of apoptosis and apoptosis-associated protein expressions. These findings demonstrate that PNS reduces CAKI through increasing HIF-1α to inhibit mitochondrial apoptosis pathway. Hence, we suggest PNS as a protective and therapeutic new drug for CDDP treatment of cancers, which might have significant meaning of further research and application potential.