Protective effect of bioactive components from Rubi fructus against oxidative damage in human ovarian granulosa cells induced by 2,2-azobis (2-methylpropionamidine) dihydrochloride.

BACKGROUND: Diminished ovarian reserve has a serious impact on female reproduction with an increasing incidence every year. An important cause of this is oxidative stress. Rubi fructus, a traditional medicinal and edible plant, has shown therapeutic effects against gynecological diseases. Vanillic acid, isoquercitrin, kaempferol-3-O-rutinoside, kaempferol-3-O-sophoroside, oleanolic acid, tormentic acid, tiliroside, and ellagic acid are the major bioactive components in R. fructus. However, studies involved in the effectiveness and mechanism of these components in oxidative stress-induced ovarian dysfunction are scarce. RESULTS: In this study, the protective mechanisms of the bioactive components were evaluated in human ovarian granulosa cells. Isoquercitrin was significantly superior to other bioactive components in relieving damage in human ovarian granulosa cells induced by 2,2-azobis (2-methylpropionamidine) dihydrochloride, considering enhanced cell viability, reduced reactive oxygen species accumulation, and improved mitochondrial membrane potential level. Isoquercitrin protected human ovarian granulosa cells from oxidative stress by regulating the enzyme activity of glutathione peroxidase, inhibiting cell apoptosis, improving the expression of genes related to oxidative stress, and ameliorating heme oxygenase 1 protein expression. CONCLUSION: Isoquercitrin, a bioactive component in R. fructus, has a significant protective effect on oxidative damage induced by 2,2-azobis (2-methylpropionamidine) dihydrochloride in human ovarian granulosa cells, providing evidence for its potential application in protecting ovarian function. © 2024 Society of Chemical Industry.

Subxiphoid and subcostal arch versus unilateral video-assisted thoracic surgery approaches to thymectomy for myasthenia gravis.

PURPOSE: Thymectomy is an important treatment for myasthenia gravis (MG). We conducted this study to compare the clinical outcomes of the recently introduced subxiphoid and subcostal arch thymectomy (SASAT) approach with those of the standard unilateral video-assisted thoracoscopic surgery (VATS). METHODS: We analyzed, retrospectively, the perioperative, and long-term outcomes of 179 consecutive MG patients (age 18-65 years), who underwent SASAT or unilateral VATS-extended thymectomy between July, 2012 and May, 2019. RESULTS: All demographic and clinical characteristics were comparable in the two groups. The median surgical time, estimated blood loss, thoracotomy conversion rate, total and chest drainage, and complications did not differ significantly between the groups. The visual analog scale (VAS) score was significantly lower in the SASAT group. Complete stable remission (CSR) was achieved in a significantly larger proportion of the SASAT group patients and was significantly higher in women than in men. The Quantitative MG score was significantly lower in the SASAT group. Patients in the MG Foundation of America Clinical Classification groups I and II achieved better remission rates than those in groups III-V. CONCLUSIONS: SASAT is a safe and feasible MG treatment, which may yield better outcomes than unilateral VATS and improve the quality of treatment.

A Comprehensive Review of the Pharmacology, Chemistry, Traditional Uses and Quality Control of Star Anise (Illicium verum Hook. F.): An Aromatic Medicinal Plant.

Illicium verum Hook. F., also known as star anise, is one of the most important plants of the genus Anise in the family Magnoliaceae. I. verum not only has the functions of warming Yang, dispersing cold, regulating Qi and relieving pain but can also be used as a condiment to increase flavor as well as reconcile and remove fish smells. Currently, 201 chemical constituents have been identified from star anise; among these, star anise oil and shikimic acid are the two most widely used and studied chemical components in star anise, with the oil accounting for a large proportion of the total. This review integrates, classifies and updates studies related to the botany, pharmacology, phytochemistry, traditional and modern uses and quality control of star anise, with a special reference to its phytochemical composition and pharmacological activity. It will provide a reference for further research on this important medicinal plant. In addition, the broad applications and research profiles of star anise essential oil and shikimic acid are highlighted. Our review indicates that the research prospects regarding star anise are very broad and worthy of further investigation.

A Review on Phytochemicals of the Genus Maytenus and Their Bioactive Studies.

The genus Maytenus is a member of the Celastraceae family, of which several species have long been used in traditional medicine. Between 1976 and 2021, nearly 270 new compounds have been isolated and elucidated from the genus Maytenus. Among these, maytansine and its homologues are extremely rare in nature. Owing to its unique skeleton and remarkable bioactivities, maytansine has attracted many synthetic endeavors in order to construct its core structure. In this paper, the current status of the past 45 years of research on Maytenus, with respect to its chemical and biological activities are discussed. The chemical research includes its structural classification into triterpenoids, sesquiterpenes and alkaloids, along with several chemical synthesis methods of maytansine or maytansine fragments. The biological activity research includes activities, such as anti-tumor, anti-bacterial and anti-inflammatory activities, as well as HIV inhibition, which can provide a theoretical basis for the better development and utilization of the Maytenus.

A Novel Flavonoid Kushenol Z from Sophora flavescens Mediates mTOR Pathway by Inhibiting Phosphodiesterase and Akt Activity to Induce Apoptosis in Non-Small-Cell Lung Cancer Cells.

The roots of Sophora flavescens (SF) are clinically used as a traditional Chinese medicine for the treatment of various lung diseases. In this study, we investigated the mechanism by which SF inhibits proliferation and induces apoptosis in non-small-cell lung cancer (NSCLC) cells. A new compound, kushenol Z (KZ), and 14 known flavonoids were isolated from SF. KZ, sophoraflavanone G, and kushenol A demonstrated potent cytotoxicity against NSCLC cells in a dose- and time-dependent manner; KZ showed a wide therapeutic window. We also found that KZ induced NSCLC cell apoptosis by increasing the Bax/Bcl-2 ratio and by activating caspase-3 and caspase-9 leading to mitochondrial apoptosis, and upregulated CHOP and activatedcaspase-7 and caspase-12, which triggered the endoplasmic reticulum stress pathway. After KZ treatment, we observed cAMP accumulation, which reflected the inhibition of cAMP-phosphodiesterase (PDE), along with the increase in PKA activity; additionally, phospho-p70 S6 kinase was downregulated. KZ also attenuated the phosphorylation of Akt and PRAS40, which was partially rescued by an Akt activator. This suggested that KZ mediated the antiproliferative activity in NSCLC cells by inhibiting the mTOR pathway through the inhibition of cAMP-PDE and Akt. These findings suggested that KZ may be used as a promising cAMP-PDE and Akt inhibitor in targeted chemotherapeutic drug development.

A natural product from Cannabis sativa subsp. sativa inhibits homeodomain-interacting protein kinase 2 (HIPK2), attenuating MPP+-induced apoptosis in human neuroblastoma SH-SY5Y cells.

Homeodomain-interacting protein kinase 2 (HIPK2) is a conserved serine/threonine kinase, which regulate transcription, cell differentiation, proliferation and apoptosis. Previous evidences indicated that HIPK2 could be involved in the pathogenesis of neurodegenerative diseases, suggesting as a novel target for Parkinson's disease (PD) therapeutic development. Herein, gene microarray analysis was performed to verify the key regulatory function of HIPK2 in PD. (Z)-methylp-hydroxycinnamate (ZMHC, 7) with other eighteen compounds were isolated from Cannabis sativa subsp. sativa, growing in Bama Yao Autonomous County, one of the five largest longevity regions of the world. Intriguingly, ZMHC was identified to bind HIPK2 with high affinity through molecular modeling and molecular dynamics (MD) simulations. Moreover, cell morphology, flow cytometry and western blot assay suggested that ZMHC inhibited HIPK2, which attenuated MPP+-induced apoptosis in SH-SY5Y cells. In conclusion, these findings discovered a natural product that inhibited HIPK2, and highlighted that ZMHC could be a potential precursor agent for future PD therapy.

New Cassane Diterpenoids from Caesalpinia sappan and their Antiplasmodial Activity.

One new cassane diterpene possessing an unusual N bridge between C-19 and C-20 named caesalsappanin R (1), as well as another new diterpene caesalsappanin S (2), were isolated from the seeds of Caesalpinia sappanwith methanol extract. Their structures were determined by spectroscopic analysis and examined alongside existing data from prior studies. Their biological activities were profiled by their antiplasmodial activity.

[A new triterpenic acid from the roots of Rosa laevigata].

This study was designed to investigate triterpenoids from the roots of Rosa laevigata Michx. The silica gel column chromatography was used to separate the chemical constituents from the roots of Rosa laevigata Michx. HPLC was used to analyze its purity and chemical constitution. Spectroscopy methods were used to determine their structures. Five constituents were isolated and identified as19α-OH-3ß-E-feruloyl corosolic acid (1), 23-hydroxy-tormentic acid (2), 2α, 3ß, 19α, 23- tetrahydroxy-12-en-28-oleanolic acid (3), 2α, 3α, 20ß- trihydroxyurs-13 (18)-en-28-oic-acid (4), 2α, 3ß, 20ß-trihydroxyurs-13 (18)-en-28-oic-acid (5). Compound 1 was assigned as a new compound, compounds 4, 5 were obtained from the genus Rosa for the first time.

[Triterpenoids from roots of Rosa laevigata].

To study the triterpenoids from the roots of Rosa laevigata. The silica gel column chromatography was used to separate the chemical constituents from the roots of Rosa laevigata Michx. HPLC was used to analyze its purity, chemical and spectroscopy methods were used to determine their structures. 12 constituents were isolated and identified as(2R, 19R)methyl 2-acetyloxy-19- hydroxyl-3-oxo-urs-12-en-28-carboxylate(1), pomonic acid (2), 18, 19-seco, 2α, 3α-dihydroxy-19-oxo-urs-11, 13(18)-dien-28-oic acid(3), swinhoeic acid (4), myrianthic acid(5), 2α, 3ß, 19α-trihydroxy-24-oxo-urs-12-en-oic acid (6), tormentic acid(7), arjunic acid (8), 1ß-hydroxyeuscaphic acid(9), quadranoside Ⅷ (10), alpinoside(11), rubuside B (12). Compounds 1-4, 6, 9, 11-12 were obtained from this plant for the first time. Compounds 2-4, 6, 11-12 were obtained from the genus Rosa for the first time.

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats.

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague-Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn(2+) and albumin levels (P<0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P<0.01). qBase(+) was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P<0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation.

Antimalarial and Antiproliferative Cassane Diterpenes of Caesalpinia sappan.

Bioassay-guided fractionation of a methanol extract of the seeds of Caesalpinia sappan led to the isolation of 12 new cassane-type diterpenes, caesalsappanins A-L (1-12). Their structures were elucidated on the basis of NMR and HRESIMS analysis, and the absolute configuration of compound 1 was determined by single-crystal X-ray crystallography. All isolated compounds were tested against a chloroquine-resistant Plasmodium falciparum strain for antiplasmodial activities and against a small panel of human cancer cell lines for antiproliferative activities. Compounds 7 and 8 displayed antimalarial activity against the chloroquine-resistant K1 strain of P. falciparum with IC50 values of 0.78 and 0.52 µM and selectivity indices of 17.6 and 16.4, respectively. Compound 10 showed antiproliferative activity against the KB cancer cell line with an IC50 value of 7.4 µM.

[Cassae-type diterpenes from seeds of Caesalpinia minax].

Fifteen cassaen-type diterpenes were isolated from the 95% ethanolic extract of the seeds of C. minax through various chromatographic techniques. Their structures were identified on the basis of spectroscopic data as pulcherralpin (1), caesalpinin ML (2), chamaetexane C (3), chamaetexane D (4), 6ß, 18-diacetoxycassan-13, 15-diene (5), neocaesalpin K (6), neocaesalpin MP (7), neocaesalpin M (8), neocaesalpin Q (9), neocaesalpin P (10), neocaesalpin R (11), caesaldekarin D (12), caesaldekarin A (13), caesaldekarin b (14), 3ß,6α-diacetoxyvouacapane (15). Among them, compounds 14, 9-11 were isolated from this plant for the first time.

Two new degradative cassane-type diterpenes isolated from Caesalpinia minax.

Cassane-type diterpenes are main bioactive constituents of Caesalpinia minax HANCE. As a part of our ongoing chemical investigation of C. minax, two new degradative cassane-type diterpenes, named caesalpins I (1) and J (2), were isolated from the EtOAc extract of the seeds of C. minax. The structures were elucidated by means of spectroscopic analysis.

A new ursane-type triterpene, cymosic acid from Rosa cymosa.

A new ursane-type triterpene, cymosic acid (1) together with two known compounds, 3ß,19α-dihydroxy-2-oxo-12-ursen-28-oic acid (2) and 2α,19α-dihydroxy-3-oxo-12-ursen-28-oic acid (3), were isolated from Rosa cymosa Tratt. The structure of compound 1 was elucidated by analyzing its ¹H and ¹³C NMR, ¹H-¹H COSY, HSQC, HMBC, NOESY, and HR-ESI-MS values. The three compounds were found to display moderate inhibitory activities against nitric oxide production in lipopolysaccharide-activated macrophage cell lines, RAW 264.7 cells.

[Triterpene constituents from Rosa cymosa Tratt].

The constituents in 95% ethanol extract of the root of Rosa cymosa Tratt were purified by column chromatography techniques, leading to isolation of eleven triterpenes. Their structures were elucidated by spectroscopic data as pomolic acid (1), fupenzic acid (2), ursolic acid (3), euscaphic acid (4), arjunic acid (5), tomentic acid (6), 3ß-E-feruloyl corosolic acid (7), 1ß-hydroxyeuscaphic acid (8), myrianthic acid (9), cecropiacic acid (10), and ilexoside B (11). Among them, compounds 3, 6-8, 10 and 11 were obtained from this plant for the first time, and compounds 7 and 10 were obtained from this genus for the first time.

Potential Molecular Mechanism of Illicium simonsii Maxim Petroleum Ether Fraction in the Treatment of Hepatocellular Carcinoma.

Traditional Chinese medicine (TCM) has been considered, for many years, an important source of medicine to treat different diseases. As a type of TCM, Illicium simonsii Maxim (ISM) is used as an anti-inflammatory, anti-bacterial, and anti-virus. Besides, ISM is also used in the treatment of cancer. In order to evaluate the anti-hepatocellular carcinoma (HCC) activity, petroleum ether extract was prepared from part of the fruit of ISM. First, the compounds of the petroleum ether fraction of Illicium simonsii Maxim (PEIM) were identified using LC-MS/MS analysis. Next, the cell viability and morphological changes were evaluated by MTT assay and Hoechst staining. In addition, the effect of PEIM on the levels of inflammatory factors (TNF-α, IL-1ß, and IL-6) was determined using the ELISA kit. Furthermore, apoptosis was evaluated by flow cytometry, and gene expression and the regulation of signaling pathways were investigated, respectively, by real-time fluorescence quantitative PCR (RT-qPCR) and western blot. Results showed that a total of 64 compounds were identified in the PEIM. Additionally, the PEIM had anti-HCC activity against HepG2 cells, in which the half maximal inhibitory concentration (IC50) was 55.03 µg·mL-1. As well, the PEIM was able to modulate the expression of TNF-α, IL-1ß, and IL-6, while we also found that it induced HepG2 cell apoptosis through the activation of P53 mRNA and caspase-3 mRNA. Finally, the PEIM possibly downregulated the expression of TLR4, MyD88, p-NF-κBp65, TNF-α, IL-1ß, INOS, IL-6, JAK2, STAT3, CyclinD1, CDK4, MDM2, and Bcl-2, and upregulated the expression of P53, P21, Bax, Cytochrome-C, Caspase-9, and Caspase-3 in HepG2 cells. These findings may confirm that the PEIM has possible anti-HCC effects. However, additional studies are required to fully understand the mechanisms of action of the PEIM and the signaling pathways involved in its effects. Moreover, the anti-HCC activity of the PEIM should be studied in vivo, and signaling pathways involved in its effects should be explored to develop the anti-HCC drug.

Rosamultin ameliorates radiation injury via promoting DNA injury repair and suppressing oxidative stress in vitro and in vivo.

Radiotherapy remains the preferred treatment option for cancer patients with the advantages of broad indications and significant therapeutic effects. However, ionizing radiation can also damage normal tissues. Unfortunately, there are few anti-radiation damage drugs available on the market for radiotherapy patients. Our previous study showed that rosamultin had antioxidant and hepatoprotective activities. However, its anti-radiation activity has not been evaluated. Irradiating small intestinal epithelial cells and mice with whole-body X-rays radiation were used to evaluate the in vitro and in vivo effects of rosamultin, respectively. Intragastric administration of rosamultin improved survival, limited leukocyte depletion, and reduced damage to the spleen and small intestine in irradiated mice. Rosamultin reversed the downregulation of the apoptotic protein BCL-2 and the upregulation of BAX in irradiated mouse small intestine tissue and in irradiation-induced small intestinal epithelial cells. DNA-PKcs antagonists reversed the promoting DNA repair effects of rosamulin. Detailed mechanistic studies revealed that rosamultin promoted Translin-associated protein X (TRAX) into the nucleus. Knockdown of TRAX reduced the protective effect of rosamultin against DNA damage. In addition, rosamultin reduced irradiation-induced oxidative stress through promoting Nrf2/HO-1 signaling pathway. To sum up, in vitro and in vivo experiments using genetic knockdown and pharmacological activation demonstrated that rosamultin exerts radioprotection via the TRAX/NHEJ and Nrf2/HO pathways.

Caesalpins A-H, bioactive cassane-type diterpenes from the seeds of Caesalpinia minax.

Eight new cassane-type diterpenes, caesalpins A-H (1-8), were isolated from the ethyl acetate extract of Caesalpinia minax. Compound 1 displayed significant antiproliferative activity against HepG-2 (IC50 4.7 µM) and MCF-7 (IC50 2.1 µM) cells, and compounds 2 and 4 exhibited selective cytotoxic activities against MCF-7 (IC50 7.9 µM) and AGS (IC50 6.5 µM) cells.

Cytotoxic constituents from Psoralea corylifolia.

Bioassay directed isolation of the EtOAc extract from a traditional Chinese medicine Psoralea corylifolia resulted in the purification of two isoflavonoids, corylifols D (1) and E (2), along with four known ones. The structures of 1 and 2 were determined by extensive 1D and 2D NMR and MS data analyses. When tested against HepG2 and Hep3B hepatocellular carcinoma cell lines, corylifol A (4) displayed IC50 values of 4.6 and 13.5 µg/ml, respectively.

Three new phenolics and other constituents from the seeds of Lithocarpus pachylepis.

Twelve phenolics, including the three new compounds balanophonin C (1), balanophonin D (2), balanophonin E (3), were isolated from the seeds of Lithocarpus pachylepis. Their structures were elucidated by various spectroscopic techniques (UV, IR, MS, 1D and 2D NMR). Compounds 1-9 were evaluated for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 and showed moderate inhibitory activities, with IC50 values ranging from 10.9 to 34.7 µM.