Research progress on ethnobotany, phytochemistry, pharmacological action, and applications of Engelhardia roxburghiana Wall: a review.

OBJECTIVES: Engelhardia roxburghiana Wall is a plant of the Juglandaceae family, and its leaves is the main part used as a medicine. It is used to relieve heat and pain, gasification, and dampness. The purpose of this review is to provide a systematic review about the botany, traditional uses, phytochemistry, pharmacology, and toxicology of this plant. KEY FINDINGS: Many compounds have been isolated and identified from the plant, including flavonoids, triterpenoids, steroids, quinones, essential oils, and other types of chemical constituents. Extensive pharmacological activities of the extracts or compounds of E. roxburghiana Wall in vivo and in vitro were mainly confirmed, including anti-cancer, anti-diabetic, anti-inflammatory, and anti-allergic effects. SUMMARY: In this paper, the botany, traditional uses, phytochemistry, and pharmacology of E. roxburghiana Wall were reviewed. In the future, E. roxburghiana Wall needs further study, such as paying more attention to quality control and the utilization on agriculture. In addition, discussing the medicinal components of decoction as well as the toxicity will also contribute to the progress of clinical trial studies.

Tetrahydropiperine, a natural alkaloid with neuroprotective effects in ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a life-threatening neurological disease with various pathological mechanisms. Tetrahydropiperine (THP) is a natural alkaloid with protective effects against multiple diseases, such as seizure, and pain. This study was to examine the impact of THP on IS and investigate its potential mechanism. MATERIAL AND METHODS: We employed network pharmacology and molecular docking techniques to identify the target proteins of THP for intervention in IS. Adult male Sprague-Dawley rats were used to create a permanent middle cerebral artery occlusion model. PC-12 cells were chosen to establish an oxygen-glucose deprivation (OGD) cell model. Disease modeling followed by nimodipine (NIMO); 3-methyladenine (3-MA) and rapamycin (RAP) interventions. Open field test, Longa score, balance beam test, and forelimb grip test were used to measure motor and neurological functions. The degree of neurological damage recovery was assessed through behavioral analysis, and cerebral infarction volume was determined using TTC staining. Morphological changes were examined through HE and Nissl staining, and ultrastructural changes in neurons were observed using transmission electron microscopy. The protein expression of autophagy and related pathways was analyzed through Western blot (WB). The appropriate hypoxia time and drug concentration were determined using CCK-8 assay, which also measured cell survival rate. RESULTS: The network pharmacology findings indicated that the impact of THP on IS was enhanced in the PI3K/Akt signaling pathway. THP demonstrated robust docking capability with proteins associated with the autophagy and PI3K/Akt/mTOR, as indicated by the molecular docking outcomes. THP significantly improved behavioral damage, reduced the area of cerebral infarction, ameliorated histopathological damage from ischemia, increase neuronal survival, and alleviated ultrastructural damage in neurons (P < 0.05). THP enhanced the survival of PC-12 cells induced by OGD and ameliorated the morphological harm to the cells (P < 0.05). THP was found to elevate the quantities of P62, LC3-Ⅰ, PI3K, P-AKt/Akt, and P-mTOR/mTOR proteins while reducing the levels of Atg7 and Beclin1 proteins. The results of transmission electron microscopy showed no autophagosomes in the THP, 3-MA, and 3-MA + THP groups. CONCLUSION: The activation of the PI3K/Akt/mTOR signaling pathway by THP inhibits autophagy and provides relief from neurological damage in IS.

Research Progress of Tamarixetin and its glycosides.

Tamarixetin and its glycosides are widely distributed in natural plants, and they are also natural flavonoid derivatives of quercetin. Its main pharmacological effects include antioxidant, anti-inflammatory, antiviral, anticancer, cardiovascular effects, etc. The pharmacokinetics showed that the distribution of direct absorption differed from that of biosynthesis. At the same time, research shows that tamarixetin is safe to use because it has little self-toxicity. In this paper, 181 articles on tamarixetin published from 1976 to 2023 are obtained from PubMed, China Knowledge Base Database, Wanfang Data, and other electronic databases. Tamarixetin is searched based on keywords, and 121 articles remain. Transformation synthesis, pharmacokinetics, pharmacological action, and structure-activity relationship of tamarixetin were reviewed.

Investigation of the Effects of Glabridin on the Proliferation, Apoptosis, and Migration of the Human Colon Cancer Cell Lines SW480 and SW620 and Its Mechanism Based on Reverse Virtual Screening and Proteomics.

Colon cancer is a relatively common malignant tumor of the digestive tract. Currently, most colon cancers originate from adenoma carcinogenesis. By screening various licorice flavonoids with anticancer effects, we found that glabridin (GBN) has a prominent anticolon cancer effect. First, we initially explored whether GBN can inhibit proliferation, migration, and invasion and induce apoptosis in SW480 and SW620 cells. Next, we exploited reverse virtual and proteomics technologies to screen out closely related target pathways on the basis of a drug and target database. At the same time, we constructed the structure of the GBN target pathway in colon cancer. We predicted that GBN can regulate the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of the rapamycin pathway (mTOR) pathway to fight colon cancer. Finally, through Western blot analysis and qRT-PCR, we verified that the expression levels of the PI3K, AKT, and mTOR proteins and genes in this pathway were significantly reduced after GBN administration. In short, the promising discovery of the anticolon cancer mechanism of GBN provides a reliable experimental basis for subsequent new drug development.

Effectiveness of adjuvant chemotherapy for elderly patients with triple-negative breast cancer.

There is little evidence determining whether elderly patients (from 70 to 90 years old) with triple-negative breast cancer could benefit from adjuvant chemotherapy (AC).  This study explores the effect of AC in these population following surgery. A total of 4610 patients were identified in the Surveillance, Epidemiology, and End Results database (2010-2018). Multiple imputation by chained equations was performed to impute missing data. Inverse probability of treatment weighting (IPTW) was applied to reduce the selection bias. IPTW-adjusted Kaplan-Meiers survival analysis and Cox proportional hazards models were performed to compare breast cancer specific survival (BCSS) and overall survival (OS) in the two treatment groups. The patients were classified into the chemotherapy (n=1989) and the observation (n=2621) groups. The percentage of patients receiving AC versus observation increased significantly from 2010 to 2018 (estimated annual percentage change, 1.49%; 95%CI, 0.75-2.16%, p=0.002). The 5-year IPTW-adjusted rates of BCSS and OS in AC group were better than that in observation group (BCSS: 82.32% vs. 78.42%, p=0.010; OS: 75.54% vs. 64.65%, p<0.001). The patients could benefit from AC based on the results of IPTW-adjusted Cox proportional hazards regression analysis (BCSS: HR, 0.77, 95%CI, 0.62-0.94, p=0.012; OS: HR, 0.66, 95%CI, 0.57-0.78, p<0.001). AC was associated with a significant outcome benefit across the year at diagnosis, marital status, stage, lymph node, surgery, and radiation subgroups (all p<0.050). Patients with T1ab could not benefit from AC (p>0.050). In conclusion, we presented a BCSS and OS benefit from AC in elderly patients with triple-negative breast cancer (TNBC). AC remained a reasonable treatment approach in these specific patients. For the patients with T1ab, de-escalated treatment would be administrated with caution.

Oncopreventive and Oncotherapeutic Potential of Licorice Chalcone Compounds: Molecular Insights.

BACKGROUND: Licorice is an important traditional Chinese medicine commonly used in clinical practice and contains more than 300 flavonoids. Chalcone is one of the main types of flavonoids with a wide range of biological functions and pharmacological activities. In the anticancer research, chalcone compounds have shown excellent performance. OBJECTIVE: This review aims to summarize the biosynthetic pathway and pharmacokinetics of chalcone from licorice and provide evidence for the anticancer effects of chalcone and the underlying mechanisms involved. METHODS: For this review, the following databases were consulted: the PubMed Database (https://pubmed.ncbi.nlm.nih.gov), Chinese National Knowledge Infrastructure (http:// www.cnki.net), National Science and Technology Library (http://www.nstl.gov.cn/), Wanfang Data (http://www.wanfangdata.com.cn/), and the Web of Science Database (http:// apps.webofknowledge.com/). RESULTS: To date, about 56 chalcones have been isolated and identified from licorice, 14 of which have antitumor effects. These chalcones have a wide range of biological activities and can inhibit the viability, proliferation, and migration of cancer cells by blocking the cancer cell cycle, thus inducing apoptosis and autophagy. However, the molecular mechanism of the anticancer effects of chalcone is not fully understood. CONCLUSION: In this paper, the molecular mechanism of chalcone regulating different types of cancer is reviewed in detail from the biosynthetic pathway. This comprehensive review article summarizes the biosynthetic pathway and pharmacokinetics of chalcone from the traditional Chinese medicine licorice and provides evidence for the potential anticancer effects of chalcone and the respective mechanisms of action. This paper also provides a basis for structural modification, biosynthesis, and new drug development of chalcone compounds in Glycyrrhiza uralensis.

Pulsatilla chinensis (Bge.) Regel: A Systematic Review on Anticancer of Its Pharmacological Properties, Clinical Researches and Pharmacokinetic Studies.

Pulsatilla chinensis (Bge.) Regel (PC) is one of the most commonly used Chinese medicines and has a history of thousands of years. This article reviews the research results of anti-cancer activity and its mechanism of action obtained from experimental, clinical, pharmacokinetic and bioinformatic studies in recent years. A large number of studies have shown that PC exerts had anti-cancer effects on different types of tumor cells by inhibiting cell proliferation, inducing apoptosis, inhibiting cell cycle and energy metabolism, inducing autophagy, and inhibiting angiogenesis. The literature has shown that PC can trigger the expression of autophagy-related molecules, activate the mitochondrial apoptotic pathway, inhibit the phosphorylation of PI3K downstream factors, down-regulate the expression of glycolysis-related proteins, and regulate a series of cancer-related signal pathways and proteins. The molecular mechanisms involved in PC include signal pathways such as Notch, PI3K/AKT/m TOR, AKT/mTOR, and MEK/ERK. The article also discusses the derivatives of the active ingredients in PC, which greatly improved the anti-cancer effect. In conclusion, this review provides a comprehensive overview of the biological effects and mechanisms of PC against cancer. The analysis of the literature shows that PC can be used as a potential drug candidate for the treatment of cancer.

Saikosaponin B4 Suppression Cancer Progression by Inhibiting SW480 and SW620 Cells Proliferation via the PI3K/AKT/mTOR Pathway in Colon Cancer.

BACKGROUND: Colon cancer is a gastrointestinal malignancy with high incidence and poor prognosis. OBJECTIVE: Saikosaponin B4 (SSB4) is a monomeric component of the Traditional Chinese medicine (TCM), Bupleurum. The current study investigates the therapeutic effect and mechanisms of SSB4 in colon cancer. METHODS: The proliferation of two colon cancer cell lines, SW480 and SW620, were assessed using CCK8 and expression of regulatory molecules, including Bax, Caspase3, Caspase9, Cleaved Caspase3, Cleaved Caspase9 and Bcl2 by flow cytometry and Western blotting. RESULTS: Survival rates, assessed by CCK8, of SW480 and SW620 cells decreased significantly when the SSB4 concentration was in the range 12.5-50 µg/ml. Flow cytometry measurements indicated apoptosis rates of 55.07% ± 1.63% for SW480 cells and 33.07% ± 1.28% for SW620 cells treated with 25 µg/ml SSB4. Western blotting revealed upregulation of the proapoptotic proteins, Bax, Caspase3, Caspase9, Cleaved Caspase3 and Cleaved Caspase9, and downregulation of the anti-apoptotic protein, Bcl2, in the presence of SSB4. Network pharmacology and molecular docking predicted that the PI3K/Akt/mTOR pathway might be the main regulatory target for the antitumor effect of SSB4. Further Western blotting experiments showed that SSB4 downregulated (p < 0.01) expression of PI3K, Akt, mTOR and the phosphorylated proteins, P-PI3K, P-Akt and P-MTOR. Expression of PI3K, Akt and mTOR mRNA was found to be downregulated by SSB4 (P < 0.01) as the result of RT-PCR measurements. CONCLUSION: SSB4 is a potent anti-colon cancer agent. Its effects are likely to be mediated by suppression of the PI3K/AKT/mTOR pathway.

Hyperoside: A Review of Its Structure, Synthesis, Pharmacology, Pharmacokinetics and Toxicity.

Hyperoside is an active ingredient in plants, such as Hypericum monogynum in Hypericaceae, Crataegus pinnatifida in Rosaceae and Polygonum aviculare in Polygonaceae. Its pharmacologic effects include preventing cancer and protecting the brain, neurons, heart, kidneys, lung, blood vessels, bones, joints and liver, among others. Pharmacokinetic analysis of hyperoside has revealed that it mainly accumulates in the kidney. However, long-term application of high-dose hyperoside should be avoided in clinical practice because of its renal toxicity. This review summarises the structure, synthesis, pharmacology, pharmacokinetics and toxicity of hyperoside.

Piperine ameliorates ischemic stroke-induced brain injury in rats by regulating the PI3K/AKT/mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Piperine (PIP), a main active component isolated from Piper nigrum L., exerts neuroprotective effects in a rat model of ischemic stroke (IS). However, studies on the effects of PIP on neuroprotection and autophagy after IS are limited. AIM OF THE STUDY: This study aimed to prove the protective effects of PIP against brain IS and elucidate its underlying mechanisms. MATERIALS AND METHODS: Specific pathogen-free male Sprague-Dawley rats were selected to establish a permanent middle cerebral artery occlusion model. The experiment was randomly divided into six groups: sham group, model group, PIP intervention group (10, 20, and 30 mg/kg group), and nimodipine group (Nimo group, 12 mg/kg). Neurological function score, postural reflex score, body swing score, balance beam test, and grip strength test were used to detect behavioral changes of rats. The area of cerebral infarction was detected by TTC staining, and the number and morphological changes of neurons were observed by Nissl and HE staining. In addition, the ultrastructure of hippocampal dentate gyrus neurons was observed using a transmission electron microscope. Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway proteins and autophagy-related proteins, namely, Beclin1 and LC3, in the hippocampus and cortex. Cell experiments established an in vitro model of oxygen-glucose deprivation (OGD) with the HT22 cell line to verify the mechanism. The experiment was divided into five groups: control group, OGD group, OGD + PIP 20 µg/mL group, OGD + PIP 30 µg/mL group, and OGD + PIP 40 µg/mL group. CCK-8 was used to measure cell activity, and Western blot was used to measure the expression of PI3K/AKT/mTOR signaling pathway proteins and autophagy-related proteins (Beclin1 and LC3). RESULTS: Compared with the model group, the neurological function scores, body swing scores, and postural reflex scores of rats in the 10, 20, and 30 mg/kg PIP intervention groups and Nimo groups decreased, whereas the balance beam score and grip test scores increased (all p < 0.05). After 10, 20, and 30 mg/kg PIP and Nimo intervention, the cerebral infarction area of pMCAO rats was reduced (p < 0.01), and Nissl and HE staining results showed that the number of neurons survived in the 30 mg/kg PIP and Nimo intervention groups increased. Cell morphology and structure were significantly improved (p < 0.05). Most of the hippocampal dentate gyrus neurons and their organelles gradually returned to normal in the 30 mg/kg PIP and Nimo intervention groups, with less neuronal damage. The expression levels of p-mTOR, p-AKT, and p-PI3K in the hippocampus and cortex of the 30 mg/kg PIP and Nimo intervention groups decreased, whereas the expression level of PI3K increased (all p < 0.05). In addition, the expression level of autophagy-related proteins, namely, Beclin1 and LC3-II, in the 30 mg/kg PIP and Nimo intervention groups decreased (all p < 0.05). Results of CCK-8 showed that after 1 h of OGD, the 30 and 40 µg/mL PIP intervention groups had higher cell viability than the OGD group (p < 0.01). Western blot results showed that compared with the OGD group, the expression level of p-mTOR, p-AKT, and p-PI3K in the 30 and 40 µg/mL PIP intervention groups decreased, and the expression level of PI3K increased (all p < 0.05). Moreover, the expression level of autophagy-related proteins, namely, Beclin1 and LC3-II, in the 30 and 40 µg/mL PIP intervention groups decreased (all p < 0.05). CONCLUSIONS: This study shows that PIP is a potential compound with neuroprotective effects. PIP can inhibit the PI3K/AKT/mTOR pathway and autophagy. Its inhibition of autophagy is possibly related to modulating the PI3K/AKT/mTOR pathway. These findings provide new insights into the use of PIP for the treatment of IS and its underlying mechanism.

Structure, Biological Activities and Metabolism of Flavonoid Glucuronides.

BACKGROUND: Flavonoid glucuronides are a kind of natural products presenting a flavone linked directly with one or several glucuronides through O-glycoside bond. They had become of interest in natural product research in the past decades for their antioxidant, anti-inflammatory, and antibacteria activities. In particular, the compound breviscapine has a notable effect on cardiocerebrovascular diseases. Several other compounds even have antitumor activity. METHODS: Through searching the database and reading a large number of documents, we summarized the related findings of flavonoid glucuronides. RESULTS: We summarized 211 naturally occurring flavonoid glucuronides in 119 references with their chemical structures, biological activities, and metabolism. A total of 220 references from 1953 to 2020 were cited in this paper according to literature databases such as CNKI, Weipu, Wanfang data, Elsevier, Springer, Wiley, NCBI, PubMed, EmBase, etc. Conclusion: Flavonoid glucuronides are a class of compounds with various chemical structures and a diverse range of biological activities. They are thought to be potential candidates for drug discovery, but the specific study on their mechanisms is still limited until now. We hope this article can provide references for natural product researchers and draw more attention to flavonoid glucuronides' biological activities and mechanisms.

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.

Circ_0001658 regulates gefitinib resistance of non-small cell lung cancer through miR-409-3p/TWIST1 axis.

To investigate the function and mechanism of circular RNA circ_0001658 on gefitinib resistance of non-small cell lung cancer (NSCLC) cells. Circ_0001658, microRNA (miRNA, miR)-409-3p and twist family bHLH transcription factor 1 (TWIST1) expression levels in NSCLC tissues and cell lines were probed by quantitative real-time PCR and Western blot assays. Cell counting kit-8 assay was adopted to examine the inhibitory effect of different concentrations of gefitinib on the viability of NSCLC cells, with the 50% concentration of inhibition (IC50) value calculated. Besides, BrdU assay and flow cytometry assay were used to detect the proliferative and apoptotic rate of NSCLC cells. What's more, the binding relationships between miR-409-3p and circ_0001658, miR-409-3p and TWIST1 mRNA 3' untranslated region (3' UTR) were confirmed by dual-luciferase reporter gene assay and RNA immunoprecipitation assay. Circ_0001658 expression was raised in NSCLC tissue samples and cell lines, which was significantly associated with TNM stage and the differentiation degree of NSCLC tissues. Knocking down circ_0001658 could restrain the viability of NSCLC cells, promote the apoptosis, and reduce the IC50 of gefitinib, while transfection of miR-409-3p inhibitors could partially reverse these impacts. Additionally, circ_0001658 directly targeted miR-409-3p and negatively modulated its expression. TWIST1 was the target of miR-409-3p, which could be indirectly and positively modulated by circ_0001658. Moreover, circ_0001658 expression was negatively interrelated with miR-409-3p expression, while positively correlated with TWIST1 expression in NSCLC samples. Circ_0001658 promotes the malignant phenotypes and the resistance to gefitinib of NSCLC cells by regulating the miR-409-3p/TWIST1 axis.

The traditional uses, phytochemistry, pharmacology and toxicology of Dictamnus dasycarpus: a review.

OBJECTIVES: Dictamnus dasycarpus is a plant of the Rutaceae family, and its root bark is the main part used as a medicine, named 'Bai-Xian-Pi'. It is used to clear away heat, remove dampness, and dispel wind and also used for detoxification. The purpose of this review is to provide a systematic review about the botany, traditional uses, phytochemistry, pharmacology and toxicology of this plant. KEY FINDINGS: More than 200 compounds have been isolated and identified from the plant, including alkaloids and their glycosides, terpenoids and their derivatives and phenylpropanoids. Extensive pharmacological activities of the extracts or compounds of D. dasycarpus in vivo and in vitro were mainly confirmed, including anti-inflammatory activity, protecting cardiovascular activity, improving liver injury and anti-cancer activity. SUMMARY: In this paper, the botany, traditional uses, phytochemistry and pharmacology of D. dasycarpus were reviewed. In the future, D. dasycarpus needs further study, such as paying more attention to quality control and the utilization on agriculture. In addition, discussing the medicinal components of decoction as well as the toxicity will also contribute to the progress of clinical trial studies.

Phlomoides umbrosa (Turcz.) Kamelin & Makhm: A review of its traditional uses, botany, phytochemistry, pharmacology and clinical research.

ETHNOPHARMACOLOGICAL RELEVANCE: Phlomoides umbrosa (Turcz.) Kamelin & Makhm (P. umbrosa, Lamiaceae) is also known as "Caosu" in China and "Han Sok-Dan" in Korea. It has been used as a traditional medicine for hundreds of years. This plant is not only as a traditional medicine to alleviate diseases such as colds, arthritis, osteoporosis, but also as a food additive. AIM OF THE STUDY: This review provides up-to-date investigations of this plant, including its botany, traditional uses, pharmacology, phytochemistry, clinical research, cytotoxicity, and safety evaluation. The possible purposes and perspectives for future research of P. umbrosa are also discussed. MATERIALS AND METHODS: Information on the studies of P. umbrosa is collected from scientific journals and reports via library and electronic data search (PubMed, Baidu Academic, Google Scholar, Science Direct, ACS, Web of Science, and CNKI). Meanwhile, it is also obtained from published works of folk records, ethnopharmacological literature, Ph.D. and Masters Dissertation. RESULTS: Phytochemical research reveals that this plant contains triterpenoids, iridoids, phenylethanoids, flavonoids, essential oil, microelement, etc. The extract of P. umbrosa exhibits extensive pharmacological activities including anti-osteoporosis, anti-allergic, anti-bacterial, anti-nociceptive, anti-inflammatory, anti-oxidant, anti-cancer. Almost no obvious toxicity or side effects is observed and recorded for P. umbrosa. CONCLUSIONS: This review summarizes traditional uses, botany, pharmacology, phytochemistry, clinical research, cytotoxicity, and safety evaluation of P. umbrosa, and presents the constituents and their corresponding chemical structures found in P. umbrosa comprehensively for the first time. Meanwhile, modern pharmacological studies also are extensively investigated at present. It is worth mentioning that P. umbrosa promotes children's growth as well as the application of clinical research. Although there are clinical studies on P. umbrosa, its pharmacokinetics needs to be further elucidated. Besides, P. umbrosa is also limited in identifying active compounds and clarifying pharmacological mechanisms. Similarly, modern researches on the traditional application of P. umbrosa should also be urgently confirmed, such as treatment of fractures and hemostasis. It is believed that this review will provide a theoretical basis and valuable data for future in-depth research and application.

Dietary profile and phenolics consumption in university students from the Ningxia Hui Autonomous Region of China.

BACKGROUND: Polyphenol intake assessment is a first step for evaluating relationships between polyphenols and health-related outcomes. Ningxia Hui Autonomous Region is one of the minority areas in China, which is primarily consists of arid, dry desert. OBJECTIVES: This study was to make assessment about phenolics intake by university students from Ningxia of China. METHODS: This study employed data from a cross-sectional survey conducted from February to June 2018 in Ningxia Hui Autonomous Region of Northwest China. A total of 413 undergraduate students (143 boys, 270 girls), mean age 20.6 years, participated in the study. Food-frequency consumption and anthropometric measurements were included in the survey. According to phenol-explorer website, the amount of different classes of phenolic compounds were established. Statistics analyses were conducted with IBM SPSS 20.0. RESULTS: Profile of the student subjects showed low weight (19.1%), overweight (6.8%) and obesity (0.5%). The mean value about phenolics intake was 1378 mg/day. The main polyphenols consumed were flavonoids (58.7% of total polyphenols), followed by phenolic acids (38.1%). Vegetables, fruits and cereals products were the most consumed foods, while infusions and sugar products were lower. Fruit was the main food sources of total polyphenols, especially apple (22.95%), orange juice (19.03%) and apple juice (3.93%). CONCLUSIONS: This is the first study on the polyphenol intake of university students in Ningxia of China. The present results will be benefit for further investigation on the role of polyphenol intake against disease occurrence for this adults group.

Dichloromethane extraction from Piper nigrum L. and P. longum L. to mitigate ischemic stroke by activating the AKT/mTOR signaling pathway to suppress autophagy.

Dichloromethane fraction (DF) of Piper nigrum L. and P. longum L. (PnL and PlL), has been found to exert a protective effect against ischemic stroke in rats. However, the regulatory mechanism exerted by PnL and PIL have not been fully elucidated. In this study, we found that DF greatly ameliorated cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion (pMCAO). The neurological score, behavioral assessment, brain infarct volume, phosphorylation of AKT (p-AKT), phosphorylation mTOR (p-mTOR), and Atg7 protein levels were determined. Additionally, we discovered that DF pretreatment reduced infarct volume, neurological score, and brain damage. Furthermore, DF therapy caused the downregulation of Atg7 and p-AKT expression, as well as the upregulation of p-mTOR expression. In conclusion, our findings indicated that DF treatment can reduce brain damage and inhibit apoptosis and autophagy by activating the Akt-mTOR signaling pathway in ischemic stroke.

Cynanchum paniculatum (Bunge) Kitag. ex H. Hara: A review of its ethnopharmacology, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum paniculatum (Bunge) Kitag. ex H. Hara (C. paniculatum), is a broadly used traditional medicinal plant by East Asians. The roots and rhizomes of this herb were named 'Xu-Chang-Qing' since the Qin or Han Dynasty (B.C.221-220) in China. It is pungent and warm in nature and associated with the liver and stomach meridians. Moreover, the efficacy of this herb are dispelling wind, resolving dampness, relieving pain and itching. It is used for treating the onset of rheumatic arthralgia, stomachache, toothache, lumbago, soft tissue injury, rubella and eczema. AIM OF THE STUDY: The purpose of this paper is to provide a systematic review about the botany, traditional uses, phytochemistry and pharmacology of C. paniculatum on the strength of the studies in the past two decades. MATERIALS AND METHODS: A comprehensive search on previous literature was conducted on databases such as Web of Science, Pubmed, Sciencedirect, American Chemical Society (ACS), Google scholar and China national knowledge internet (CNKI). The search was based on the botany, traditional uses, phytochemistry and pharmacology of C. paniculatum. The key search words were 'Cynanchum paniculatum' and 'Radix Cynanchi Paniculati'. In addition, some published books were searched for more information on the herb. RESULTS: Over 150 compounds have been isolated and identified from C. paniculatum, including C21 steroids, volatile oils, carbohydrates and phenanthroindolizidine alkaloids. Extensive pharmacological activities of the extracts or compounds of C. paniculatum in vivo and in vitro were confirmed including anti-inflammatory, anti-nociceptive, sedative antiviral, antitumor, neuroprotective, treating snake bites, immunomodulatory, anti-radiation, vasodilatory, acaricidal potentials and anti-adipogenic activities. CONCLUSIONS: In this paper, the botany, traditional uses, phytochemistry and pharmacology of C. paniculatum were reviewed. This herb has long been used as traditional medicine. It was reported with numerous chemical ingredients and various pharmacological activities with anti-inflammatory, antitumor, neuroprotection, etc. In the future, C. paniculatum still needs further study, such as identifying the active compounds, clarifying the pharmacological mechanisms, discussing quality and safety.

Helicobacter pylori antibiotic eradication coupled with a chemically defined diet in INS-GAS mice triggers dysbiosis and vitamin K deficiency resulting in gastric hemorrhage.

Infection with Helicobacter pylori causes chronic inflammation and is a risk factor for gastric cancer. Antibiotic treatment or increased dietary folate prevents gastric carcinogenesis in male INS-GAS mice. To determine potential synergistic effects, H. pylori-infected male INS-GAS mice were fed an amino acid defined (AAD) diet with increased folate and were treated with antibiotics after 18 weeks of H. pylori infection. Antibiotic therapy decreased gastric pathology, but dietary folate had no effect. However, the combination of antibiotics and the AAD diet induced anemia, gastric hemorrhage, and mortality. Clinical presentation suggested hypovitaminosis K potentially caused by dietary deficiency and dysbiosis. Based on current dietary guidelines, the AAD diet was deficient in vitamin K. Phylloquinone administered subcutaneously and via a reformulated diet led to clinical improvement with no subsequent mortalities and increased hepatic vitamin K levels. We characterized the microbiome and menaquinone profiles of antibiotic-treated and antibiotic-free mice. Antibiotic treatment decreased the abundance of menaquinone producers within orders Bacteroidales and Verrucomicrobiales. PICRUSt predicted decreases in canonical menaquinone biosynthesis genes, menA and menD. Reduction of menA from Akkermansia muciniphila, Bacteroides uniformis, and Muribaculum intestinale were confirmed in antibiotic-treated mice. The fecal menaquinone profile of antibiotic-treated mice had reduced MK5 and MK6 and increased MK7 and MK11 compared to antibiotic-free mice. Loss of menaquinone-producing microbes due to antibiotics altered the enteric production of vitamin K. This study highlights the role of diet and the microbiome in maintaining vitamin K homeostasis.

Effects of dietary replacement of fish oil by vegetable oil on proximate composition and odor profile of hepatopancreas and gonad of Chinese mitten crab (Eriocheir sinensis).

Five different diets with different ratio of fish oil to vegetable oil were prepared. The biological index and proximate composition of Eriocheir sinensis fed with different diets were compared, and then sensory analysis, electronic nose (E-nose) and headspace-solid phase micro-extraction combined with gas chromatography-mass spectrometer (HS-SPME-GC-MS) analysis were applied to determine the odor profile of E. sinensis. The results showed that partial replacement (50%-75%) of fish oil by vegetable oil (FO/VO) was beneficial to the weight increment, nutrition accumulation, and odor-active compounds (OACs) formation of E. sinensis. A total of 7 and 11 OACs were detected in the hepatopancreas and gonad, respectively, these OACs contributed greatly to the overall odor profiles of E. sinensis when the dietary replacement levels were at 50% and 75%, respectively. The results could provide the guide for dietary fish oil replacement as well as improving the odor quality of E. sinensis. Practical application The objective of this research is to compare the effects of dietary replacement of fish oil by vegetable oil on proximate composition and odor profiles of E.sinensis. The results obtained from this study would not only chose an optimal dietary replacement level and serve as a useful database for the odor of female and crabs, but also provide some guide for the improvement of Chinese mitten crab aquaculture.