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.

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.

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.

Two new triterpenes isolated from Maytenus guangxiensis C. Y. Cheng et W. L. Sha and their antiproliferative activities.

Two new triterpenes, 3ß, 7ß-dihydroxyolean-12-en-11-one (1) and 3ß-O-acetyl-7ß-hydroxyolean-12-en-11-one (2), along with four known triterpenes 3ß-hydroxyolean-12-en-11-one (3), ß-amyrin (4), lup-20(29)-ene-1ß, 3ß-diol (5) and 1ß, 3ß-dihydroxy-urs-9(11)-12-diene (6), were isolated from the stems and leaves of Maytenus guangxiensis C. Y. Cheng et W. L. Sha. Their structures were elucidated using 1D and 2D NMR spectroscopy as well as MS and IR experiments. Compounds (3-6) were isolated from M. guangxiensis for the first time. Compounds 1-6 were evaluated for their antiproliferative activities against Eca-109, PANC-1, EJ and HeLa cell lines. The results showed that compounds 1-6 displayed a certain degree of inhibitory effects against the proliferation of various human cancer cell lines.

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.

Traditional uses, phytochemical, pharmacology, quality control and modern applications of two important Chinese medicines from Rosa laevigata Michx.: A review.

Rosa laevigata Michx. is an ethnic medicine that have strong biological activities used in the traditional medicine system for the treatment of diabetes, nephropathy, myocardial damage, oxidative damage, liver damage and so on. Currently, The Chinese herb R. laevigata Michx. can be divided into two important medicines: Fructus R. laevigata and Radix R. laevigata, from which approximately 148 chemical components have been isolated, including flavonoids, lignans, polyphenols, steroids, triterpenoids, tannins as well as other components. Pharmacological studies have already confirmed that both of these herbs have antioxidant, anti-inflammatory, antiviral and anti-tumor activities, as well as renal protective, immunomodulatory, lipid-lowering, cardiovascular protective, bacteriostatic, and other pharmacological effects. Toxicological tests and quality control studies revealed the safety and nontoxicity of R. laevigata Michx. Therefore, this paper systematically summarizes the traditional uses, botanical, phytochemical, and pharmacology as well as the quality control and toxicology of Fructus and Radix, which in order to provide a comprehensive reference for its continued research.

Three new cadinane-type sesquiterpenes from Eupatorium adenophorum spreng.

Three new cadinane-type sesquiterpenes, eupatorinones A-C (1-3), along with seven known compounds (4-10), were obtained from the petroleum ether fraction of 95% ethanol extract of Eupatorium adenophorum Spreng. The structures of these new compounds were determined by NMR, MS, and ECD spectra analysis. The configuration of compound 3 was established by quantum chemical calculations of NMR chemical shifts and ECD spectra, that matched the experimental data. In addition, compounds 1, 3 and 5 increased the glucose uptake in L6 cells by 1.42, 1.21 and 1.60 times, respectively.[Formula: see text].

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.

Data of cytotoxicity, p53 and Akt downstream proteins and physiological indexes in hepatocellular carcinoma cells or HepG2-bearing nude mouse model administered by α-Humulene.

This data article contains data related to the research article entitled "α-Humulene inhibits hepatocellular carcinoma (HCC) cell proliferation and induces apoptosis through the inhibition of Akt signaling" (Chen et al., 2019) [1]. The article focuses on the antiproliferation of α-Humulene (HML) and the mechanisms involved in HCC cells inhibition. In this data, cytotoxicity of HML in several HCC cell lines are reported, together with the changes in proteins involving in p53 and Akt downstream. Weight curve, blood biochemical parameters and organ indices from HepG2-bearing nude mouse model are also provided, suggesting the potential side effects in HML administration.

Anti-inflammatory and cytotoxic carbazole alkaloids from Murraya kwangsiensis.

Chemical investigation of the traditional Chinese medicine, Murraya kwangsiensis, led to the isolation of 16 undescribed biscarbazole alkaloids, kwangsines A-M, two undescribed natural products, (+/-)-bispyrayafoline C, and 19 known monomeric analogues. (±)-Bispyrayafoline C and (±)-kwangsines A-C are four pairs of biscarbazole atropisomers, and they were separated by chiral HPLC to obtain the optically pure compounds. The structures of the undescribed compounds were elucidated on the basis of HRESIMS and NMR data analysis. Their absolute configurations were assigned via comparison of the specific rotation, ECD exciton coupling method, as well as comparison of experimental and calculated ECD data. A compound showed significant inhibition on NO production in lipopolysaccharide-stimulated BV-2 microglial cells, and four compounds exhibited moderate cytotoxicities against HepG2 cells, with IC50 values less than 20 µM.

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.

α-Humulene inhibits hepatocellular carcinoma cell proliferation and induces apoptosis through the inhibition of Akt signaling.

Hepatocellular carcinoma (HCC) is a prevalent malignancy and a leading cause of cancer-related mortality. α-Humulene (HML) is a natural 11-membered monocyclic terpene with three E-configured double bonds isolated from Eupatorium odoratum L. We recently showed that HML has significant anti-HCC activity in vitro and in vivo. We found that HML was cytotoxic to HCC cells and induced mitochondrial apoptosis of HCC cells, promoting caspase-3 activation and PARP cleavage. HCC cells show abnormal Akt signaling to resist apoptosis. Mechanistically, HML was found to inhibit Akt activation, subsequently decreasing GSK-3 and Bad phosphorylation, promoting apoptotic induction. HML also inhibited cell proliferation and enhanced apoptosis in HCC tumor xenografts further highlighting its activity in vivo. Although HML showed minimal cytotoxicity to normal hepatocytes, weight loss was observed in mice administered HML. Taken together, these data provide important and novel insights into the anti-HCC effects of HML through its ability to inhibit Akt, reduced HCC cell proliferation, and enhanced HCC cell apoptotic induction in vitro and in vivo.

Essential Oil Derived From Eupatorium adenophorum Spreng. Mediates Anticancer Effect by Inhibiting STAT3 and AKT Activation to Induce Apoptosis in Hepatocellular Carcinoma.

Eupatorium adenophorum Spreng. (EA) is a well-known noxious invasive species. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the essential oil derived from EA (EAEO) is mainly composed of sesquiterpenes. However, the pharmacological value of EAEO in hepatocellular carcinoma (HCC) remains largely unexplored. Herein, we investigated the anti-HCC activities of EAEO, and explored the potential mechanisms of EAEO-induced apoptosis. An MTT assay showed that EAEO inhibited HCC cell proliferation with little toxicity on normal liver cells. Wound healing and FACS assays revealed that EAEO suppressed HCC cell migration and arrested cell cycle, respectively. Moreover, EAEO promoted in vitro HCC cell apoptosis, and EAEO treatment inhibited HepG2 xenografts growth and enhanced apoptotic nucleus of xenografts in HepG2-bearing nude mice. Mechanistically, EAEO significantly decreased the ratio of Bcl-2/Bax and resulted in the activation of caspase-9 and -3. EAEO also reduced the expression of Grp78, which in turn relieved the inhibition of caspase-12 and -7. Meanwhile, EAEO suppressed the phosphorylation of STAT3 and AKT, indicative of its anti-HCC potential. In summary, we determined that EAEO treatment promoted HCC apoptosis via activation of the apoptotic signaling pathway in mitochondria and endoplasmic reticulum, as well as repressed the activity of STAT3 and AKT in HCC cells.

Evaluation of extracts prepared from 16 plants used in Yao ethnomedicine as potential anticancer agents.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicines of the Yao ethnic group in China are a special branch of traditional Chinese medicine (TCM) and are well documented for use in disease prevention. According to an ethnopharmacological survey, there are 1392 species of medicinal plants that have been documented as Yao ethnomedicines and 104 of these species are used routinely. This study evaluated a partial collection of these 104 core plant species for their potential as anticancer agents. MATERIAL AND METHODS: A literature study of scientific journals and books in the local language was conducted. Based on an ethnopharmacological survey, 16 plant species widely used in Yao ethnomedicine were collected and 64 plant extracts were prepared from these plants. in vitro cytotoxicity screening was conducted with a panel of four human cancer cell lines, lung cancer A549, breast cancer BT20 and MCF-7, bone cancer U2OS. The potential toxicity of the extracts was evaluated using two normal human cell lines, human peripheral lung epithelial cells (HPL1A) and human umbilical vein endothelial cells (HUVEC). Additionally, the 10 extracts that demonstrated cytotoxicity in cancer cells with an IC50 of less than 25.0µg/mL were examined for the ability to induce apoptosis in U2OS cells. RESULTS: The up-to-date information regarding the traditional uses, pharmacological and biological activities, as well as the chemical constituents of the 16 plants are presented. Extracts from all 16 plants showed cytotoxicity against one to four of the human cancer cell lines and the cytotoxic effects of extracts from Melaleuca leucadendra, Stephania longa, Microsorium fortune and Bidens biternata were demonstrated for the first time. The highest anticancer potential was observed for extracts prepared from Melaleuca leucadendra Linn against all tested cancer cells (BT20, A549, U2OS, and MCF7) with an IC50 range of 3.1-32.7µg/mL. The selectivity index of the active samples varied from 0.1 to 25, and five extracts from Bidens biternata, Wedelia calendulacea, Stephania longa and Achras zapota showed significant selectivity against cancer cell lines versus normal cell lines. All tested extracts induced apoptosis in U2OS cells, and for the first time extracts from Melaleuca leucadendra and Microsorium fortune were shown to induce apoptosis. CONCLUSION: We demonstrated the in vitro anticancer efficacy and safety of 16 medicinal plants that have been historically used in Yao ethnomedicine. This study provides evidence to assist the clinical practice of Yao ethnomedicine and the development of chemotherapeutic agents from extracts prepared from these plants.

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 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.

[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.

Taurine zinc solid dispersions enhance bile-incubated L02 cell viability and improve liver function by inhibiting ERK2 and JNK phosphorylation during cholestasis.

Dietary intakes of taurine and zinc are associated with decreased risk of liver disease. In this study, solid dispersions (SDs) of a taurine zinc complex on hepatic injury were examined in vitro using the immortalized human hepatocyte cell line L02 and in a rat model of bile duct ligation. Sham-operated and bile duct ligated Sprague-Dawley rats were treated with the vehicle alone or taurine zinc (40, 80, 160mg/kg) for 17days. Bile duct ligation significantly increased blood lipid levels, and promoted hepatocyte apoptosis, inflammation and compensatory biliary proliferation. In vitro, incubation with bile significantly reduced L02 cell viability; this effect was significantly attenuated by pretreatment with SP600125 (a JNK inhibitor) and enhanced when co-incubated with taurine zinc SDs. In vivo, administration of taurine zinc SDs decreased serum alanine aminotransferase and aspartate aminotransferase activities in a dose-dependent manner and attenuated the increases in serum total bilirubin, total cholesterol and low density lipoprotein cholesterol levels after bile duct ligation. Additionally, taurine zinc SDs downregulated the expression of interleukin-1ß and inhibited the phosphorylation of Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase2 (ERK2) in the liver after bile duct ligation. Moreover, taurine zinc SDs had more potent blood lipid regulatory and anti-apoptotic effects than the physical mixture of taurine and zinc acetate. Therefore, we speculate that taurine zinc SDs protect liver function at least in part via a mechanism linked to reduce phosphorylation of JNK and ERK2, which suppresses inflammation, apoptosis and cholangiocyte proliferation during cholestasis.

Cassane diterpenes with oxygen bridge from the seeds of Caesalpinia sappan.

The seeds of the medicinal plant Caesalpinia sappan yielded fourteen cassane-type diterpenes, including six new rearranged ones named as caesalppans A-F (1-6). Their structures were elucidated by spectroscopic analysis and comparison with literature data. The isolated new compounds 1-6 possess lactone-type cassane diterpenoid skeleton with an oxygen bridge between C-19 and C-20, and were tested cytotoxic activity against four cancer cell lines using the MTT method.