Research Progress on the Synergistic Anti-Tumor Effect of Natural Anti-Tumor Components of Chinese Herbal Medicine Combined with Chemotherapy Drugs.

The application of chemotherapy drugs in tumor treatment has a long history, but the lack of selectivity of drugs often leads to serious side effects during chemotherapy. The natural anti-tumor ingredients derived from Chinese herbal medicine are attracting increased attention due to their diverse anti-tumor effects, abundant resources, and minimal side effects. An effective anti-tumor strategy may lie in the combination of these naturally derived anti-tumor ingredients with conventional chemotherapy drugs. This approach could potentially inhibit tumor growth and the development of drug resistance in tumor cells while reducing the adverse effects of chemotherapy drugs. This review provides a comprehensive overview of the combined therapy strategies integrating natural anti-tumor components from Chinese herbal medicine with chemotherapy drugs in current research. We primarily summarize various compounds in Chinese herbal medicine exhibiting natural anti-tumor activities and the relevant mechanisms in synergistic anti-tumor combination therapy. The focus of this paper is on underlining that this integrative approach, combining natural anti-tumor components of Chinese herbal medicine with chemotherapy drugs, presents a novel cancer treatment methodology, thereby providing new insights for future oncological research.

Therapeutic potential of toosendanin: Novel applications of an old ascaris repellent as a drug candidate.

Toosendanin (TSN), extracted from Melia. toosendan Sieb.et Zucc. and Melia. azedarach L., has been developed into an ascaris repellent in China. However, with the improvement of public health protection, the incidence of ascariasis has been reduced considerably, resulting in limited medical application of TSN. Therefore, it is questionable whether this old ascaris repellent can develop into a drug candidate. Modern studies have shown that TSN has strong pharmacological activities, including anti-tumor, anti-botulinum, anti-viral and anti-parasitic potentials. It also can regulate fat formation and improve inflammation. These researches indicate that TSN has great potential to be developed into a corresponding medical product. In order to better development and application of TSN, the availability, pharmacodynamics, pharmacokinetics and toxicology of TSN are summarized systematically. In addition, this review discusses shortcomings in the current researches and provides useful suggestions about how TSN developed into a drug candidate. Therefore, this paper illustrates the possibility of developing TSN as a medical product, aimed to provide directions for the clinical application and further research of TSN.

Glabridin Ameliorates Alcohol-Caused Liver Damage by Reducing Oxidative Stress and Inflammation via p38 MAPK/Nrf2/NF-κB Pathway.

Licorice is a traditional and versatile herbal medicine and food. Glabridin (Gla) is a kind of isoflavone extracted from the licorice root, which has anti-obesity, anti-atherosclerotic, and antioxidative effects. Alcoholic liver disease (ALD) is a widespread liver disease induced by chronic alcohol consumption. However, studies demonstrating the effect of Gla on ALD are rare. The research explored the positive effect of Gla in C57BL/6J mice fed by the Lieber-DeCarli ethanol mice diet and HepG2 cells treated with ethanol. Gla alleviated ethanol-induced liver injury, including reducing liver vacuolation and lipid accumulation. The serum levels of inflammatory cytokines were decreased in the Gla-treated mice. The reactive oxygen species and apoptosis levels were attenuated and antioxidant enzyme activity levels were restored in ethanol-induced mice by Gla treatment. In vitro, Gla reduced ethanol-induced cytotoxicity, nuclear factor kappa B (NF-κB) nuclear translocation, and enhanced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation. Anisomycin (an agonist of p38 MAPK) eliminated the positive role of Gla on ethanol-caused oxidative stress and inflammation. On the whole, Gla can alleviate alcoholic liver damage via the p38 MAPK/Nrf2/NF-κB pathway and may be used as a novel health product or drug to potentially alleviate ALD.

Mechanism of Yangxin Tongmai Decoction in the Treatment of Coronary Heart Disease with Blood Stasis Syndrome Based on Network Pharmacology and Molecular Docking.

This study aimed to explore the mechanism of Yangxin Tongmai decoction (YXTMD) in the treatment of coronary heart disease (CHD) with blood stasis syndrome (BSS) using network pharmacology and molecular docking, and to verify these results through clinical trials. The active compounds of YXTMD were identified using the Traditional Chinese Medicine Systems Pharmacology database, and the targets of the active compounds were predicted using the SwissTarget Prediction database. The targets of CHD and BSS were predicted using the GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases. The common targets of "herb-disease-phenotype" were obtained using a Venn diagram, then used Cytoscape software 3.8.2 and its plug-in CytoNCA and STRING database to construct the "herb active compounds-common target" and protein-protein interaction networks. R language software and bioconductor plug-in were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. AutoDock was used for the molecular docking analysis. Finally, clinical trials were conducted to confirm the results of network pharmacology. Eighty-three active components were obtained, and the core active components were 5,7,4'-trimethoxyflavone, tetramethoxyluteolin, isosinensetin, sinensetin, and 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one. A total of 140 common targets were identified, and the core targets were EGFR, VEGFA, AKT1, STAT3, TP53, ERBB2, and PIK3CA. Biological processes identified by the GO analysis primarily involved wound healing, regulation of body fluid levels, and vascular process in circulatory system. The cellular components were primarily located in the membrane raft, membrane microdomain, and plasma membrane raft. The primary molecular functions were activity of transmembrane receptor protein kinase, transmembrane receptor protein tyrosine kinase, and protein tyrosine kinase. KEGG analysis showed that the PI3K-Akt signaling pathway was closely related to the treatment of CHD with BSS by YXTMD. Molecular docking results showed that the core active components had a good binding activity with the core targets. The clinical trial results showed that YXTMD improved the BSS scores and decreased the serum levels of total cholesterol and low-density lipoprotein cholesterol. Moreover, the levels of PI3k and AKt mRNA were upregulated and the levels of GSK-3ß mRNA were downregulated. YXTMD has multicomponent, multitarget, and multipathway effects in the treatment of CHD with BSS, and its mechanism of action may involve activation of the PI3K-AKt signaling pathway, downregulation of GSK-3ß, and mediation of in vivo lipid metabolism-based metabolic processes.

Effect and Mechanism of Pharmaceutical Excipients on Berberine to Alleviate Ulcerative Colitis via Regulating Gut Microbiota.

BACKGROUND: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. METHODS: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. RESULTS: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1ß, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. CONCLUSIONS: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs' therapeutic efficiency outcome.

An EjbHLH14-EjHB1-EjPRX12 module is involved in methyl jasmonate alleviation of chilling-induced lignin deposition in loquat fruit.

Loquat fruit are susceptible to chilling injuries induced by postharvest storage at low temperature. The major symptoms are increased lignin content and flesh firmness, which cause a leathery texture. Pretreatment with methyl jasmonate (MeJA) can alleviate this low-temperature-induced lignification, but the mechanism is not understood. In this study, we characterized a novel class III peroxidase, EjPRX12, and studied its relationship to lignification. Transcript levels of EjPRX12 were attenuated following MeJA pretreatment, consistent with the reduced lignin content in fruit. In vitro enzyme activity assay indicated that EjPRX12 polymerized sinapyl alcohol, and overexpression of EjPRX12 in Arabidopsis promoted lignin accumulation, indicating that it plays a functional role in lignin polymerization. We also identified an HD-ZIP transcription factor, EjHB1, repressed by MeJA pretreatment, which directly bound to and significantly activated the EjPRX12 promoter. Overexpression of EjHB1 in Arabidopsis promoted lignin accumulation with induced expression of lignin-related genes, especially AtPRX64. Furthermore, a JAZ-interacting repressor, EjbHLH14, was characterized, and it is proposed that MeJA pretreatment caused EjbHLH14 to be released to repress the expression of EjHB1. These results identified a novel regulatory pathway involving EjbHLH14-EjHB1-EjPRX12 and revealed the molecular mechanism whereby MeJA alleviated lignification of loquat fruit at low temperature.

[Effect of auricular point sticking therapy on perioperative pain in patients with partial lung resection].

OBJECTIVE: To observe the analgesic effect of auricular point sticking therapy during the perioperative stage in the patients with partial lung resection. METHODS: A total of 92 patients with partial lung resection were randomized into an auricular point group (31 cases, 1 case dropped off), the sham-auricular point group (30 cases) and a medication group (31 cases, 1 case dropped off). The routine medication for analgesia was provided in all of the three groups. In the auricular point group, 1 day before operation, the auricular point sticking therapy was applied at shenmen (TF4), sympathetic (AH6a), subcortex (AT4), brain stem (AT3,4i), anterior ear lobe (LO4), chest (AH10) and lung (CO14), retained till the third day after operation. In the sham-auricular point group, the auricular adhesive tape without semen vaccariae was used at the same points as the auricular point group. Separately, the scores of visual analogue scale (VAS) in 8, 16, 24, 48 h and 72 h after operation, the time for obtaining the mean of the postoperative VAS score<3 points, the scores of hospital anxiety and depression scale (HAD) in 8, 72 h after operation and the plasma concentration of ß-endorphin in 24, 48 h after operation, as well as the adverse reactions after operation were recorded in the patients of each group. RESULTS: In 8, 16, 24, 48 h and 72 h after operation, VAS scores in the auricular point group were lower than those in the sham-auricular point group and the medication group separately (P<0.05). In the auricular point group, 16 h after operation the mean of VAS score was less than 3 points, but in the sham-auricular point group and the medication group, 48 h after operation, such a mean score of VAS was obtained. In 8, 72 h after operation, HAD score in the auricular point group was lower than that in the sham-auricular point group and the medication group respectively. In 24, 48 h after operation, the concentration of plasmaß-endorphin was all higher than that in the sham-auricular point group and the medication group respectively (P<0.05). In 24 h after operation, the plasma concentration ofß-endorphin in the sham-auricular point group was higher than the medication group (P<0.05). The incidence of adverse reaction in the auricular point group was lower than that in the sham-auricular point group and the medication group respectively (P<0.05). CONCLUSION: Auricular point sticking therapy relieves perioperative pain, shortens analgesic time, releases anxious and depressive emotions and reduces postoperative adverse reaction in the patients with partial lung resection. The analgesic mechanism is probably related to the increase of plasma concentration of ß-endorphin.

The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial.

Importance: It remains uncertain whether vitamin C routinely used with oral iron supplements is essential for patients with iron deficiency anemia (IDA). Objective: To compare the equivalence and assess the safety of oral iron supplements plus vitamin C or oral iron supplements alone in patients with IDA. Design, Setting, and Participants: This single-center, open-label, equivalence randomized clinical trial was conducted from January 1, 2016, to December 30, 2017, in Huashan Hospital, Fudan University. Adult patients with newly diagnosed IDA were enrolled. Participants were randomly assigned (1:1) to the oral iron supplements plus vitamin C group or the oral iron supplements-only group. Data analysis was performed from March to December 2018. Interventions: Patients were randomized to receive a 100-mg oral iron tablet plus 200 mg of vitamin C or a 100-mg iron tablet alone every 8 hours daily for 3 months. Main Outcomes and Measures: The primary outcome was the change in hemoglobin level from baseline to 2 weeks of treatment, and an equivalence margin of 1 g/dL in hemoglobin was chosen for the demonstration of comparable efficacy. Secondary outcomes included the change in the reticulocyte percentage after 2 weeks of treatment, the increase in hemoglobin level after 4 weeks of treatment, the increase in serum ferritin level after 8 weeks of treatment, and adverse events. Results: Among the 440 randomized patients (220 each in the oral iron supplements plus vitamin C group and iron-only group; 426 women [96.8%]; mean [SD] age, 38.3 [11.7] years), all were assessed for the primary outcome, and 432 (98.2%) completed the trial. From baseline to the 2-week follow-up, the mean (SD) change in hemoglobin level was 2.00 (1.08) g/dL in the oral iron supplements plus vitamin C group and 1.84 (0.97) g/dL in the oral iron supplements-only group (between-group difference, 0.16 g/dL; 95% CI, -0.03 to 0.35 g/dL), thus meeting the criteria for equivalence. The mean (SD) change in serum ferritin level from baseline to 8-week follow-up was 35.75 (11.52) ng/mL in the vitamin C plus iron group and 34.48 (9.50) ng/mL in the iron-only group (between-group difference, 1.27 ng/mL; 95% CI, -0.70 to 3.24 ng/mL; P = .21). There were no significant differences between the 2 groups regarding the rates of adverse events (46 [20.9%] vs 45 [20.5%]; difference, 0.4%; 95% CI, -6.7% to 8.5%; P = .82). No patient withdrew because of adverse events. Conclusions and Relevance: Among patients with IDA, oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption. These findings suggest that on-demand vitamin C supplements are not essential to take along with oral iron supplements for patients with IDA. Trial Registration: ClinicalTrials.gov Identifier: NCT02631668.

Effect of scar-producing moxibustion at the acupoints Zusanli (ST 36) and Feishu (BL 13) on neutrophil-to-lymphocyte ratio and quality of life in patients with non-small-cell lung cancer: A randomized, controlled trial.

OBJECTIVE: To evaluate the effect of heat stimulation via scar-producing moxibustion at the acupoints Zusanli (ST 36) and Feishu (BL 13) on the neutrophil-to-lymphocyte ratio (NLR) and quality of life in patients with non-small-cell lung cancer (NSCLC). METHODS: Seventy patients with NSCLC were randomly assigned into two groups: group A received scar-producing moxibustion at the acupoints Zusanli (ST 36) and Feishu (BL 13) every day for 6 weeks, while group B received no intervention (control group). Outcome measures were the NLR and the scores from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The NLR and the EORTC QLQ-C30 were assessed at baseline and at the end of 6 weeks. RESULTS: Five participants dropped out, leaving a final total of 65 participants who completed the trial. Groups A and B had a similar mean NLR at baseline. After the treatment course, the NLR in group A was significantly lower than that in group B (P < 0.001). Compared with group B, the EORTC QLQ-C30 scores in group A were significantly greater in terms of global health status or quality of life (P < 0.001) and function (P < 0.05), and significantly lower in terms of symptoms (P < 0.05). CONCLUSION: The present study suggests that performing scar-producing moxibustion by heat-stimulating the acupoints Zusanli (ST 36) and Feishu (BL 13) effectively decreases the NLR and improves the quality of life in patients with NSCLC.

[Impact on neutrophil-to-lymphocyte ratio and quality of life in the patients of non-small-cell lung cancer treated with grain-size moxibustion: a randomized controlled trial].

OBJECTIVE: To explore the impact on neutrophil-to-lymphocyte ratio (NLR) and the quality of life (QOL) in the patients of non-small-cell lung cancer (NSCLC) treated with wheat-size moxibustion therapy. METHODS: Seventy patients of NSCLC were randomized into an observation group and a control group, 35 cases in each one. Finally, 33 cases were participated in the observation group and 32 cases in the control group for statistical analysis. In the observation group, Zusanli (ST 36) and Feishu (BL 13) were selected for grain-size moxibustion, 9 moxa cones on each acupoint, once a day. There was the follow-up visit without any treatment applied in the control group. The trial lasted for 6 weeks. The changes in NLR and the QOL score before and after treatment were observed in the patients of the two groups and the differences were compared between the two groups. RESULTS: Compared with the condition before treatment, in the observation group, NLR was reduced apparently (P< 0.05), the general health state/life quality field, physical functioning, emotional functioning, cognitive functioning, fatigue, pain, short breath, insomnia and anorexia were improved apparently (all P < 0.05). In the control group, the differences were not significant in NLR, the general health states/life quality field, physical functioning, emotional functioning, cognitive functioning, role functioning, social functioning, fatigue, pain, short breath, insomnia and anorexia before and after treatment (all P > 0.05). In comparison of the two groups, NLR was reduced apparently in the observation group as compared with that in the control group after treatment (P < 0.05). The scores of the general health state/life quality field, physical functioning, emotional functioning and cognitive functioning were increased apparently as compared with those in the control group after treatment (all P < 0.05). The scores of fatigue, pain, short breath, insomnia and anorexia in the observation group were reduced apparently as compared with those in the control group after treatment (all P < 0.05). CONCLUSION: The wheat-size moxibustion therapy reduces NLR and improves the immune function and quality of life in the patients of NSCLC.

Acupuncture and vitamin B12 injection for Bell's palsy: no high-quality evidence exists.

OBJECTIVE: To assess the efficacy of acupuncture combined with vitamin B12 acupoint injection versus acupuncture alone to reduce incomplete recovery in patients with Bell's palsy. DATA RETRIEVAL: A computer-based online retrieval of Medline, Web of Science, CNKI, CBM databases until April 2014 was performed for relevant trials, using the key words "Bell's palsy or idiopathic facial palsy or facial palsy" and "acupuncture or vitamin B12 or methylcobalamin". STUDY SELECTION: All randomized controlled trials that compared acupuncture with acupuncture combined with vitamin B12 in patients with Bell's palsy were included in the meta-analysis. The initial treatment lasted for at least 4 weeks. The outcomes of incomplete facial recovery were monitored. The scoring index varied and the definition of healing was consistent. The combined effect size was calculated by using relative risk (RR) with 95% confidence interval (CI) using the fixed effect model of Review Manager. MAIN OUTCOME MEASURES: Incomplete recovery rates were chosen as the primary outcome. RESULTS: Five studies involving 344 patients were included in the final analysis. Results showed that the incomplete recovery rate of Bell's palsy patients was 44.50% in the acupuncture combined with vitamin B12 group but 62.57% in the acupuncture alone group. The major acupoints were Taiyang (EX-HN5), Jiache (ST6), Dicang (ST4) and Sibai (ST2). The combined effect size showed that acupuncture combined with vitamin B12 was better than acupuncture alone for the treatment of Bell's palsy (RR = 0.71, 95%CI: 0.58-0.87; P = 0.001), this result held true when 8 patients lost to follow up in one study were included into the analyses (RR = 0.70, 95%CI: 0.58-0.86; P = 0.0005). In the subgroup analyses, the therapeutic effect in patients of the electroacupuncture subgroup was better than in the non-electroacupuncture subgroup (P = 0.024). There was no significant difference in the incomplete recovery rate by subgroup analysis on drug types and treatment period. Most of the included studies were moderate or low quality, and bias existed. CONCLUSION: In patients with Bell's palsy, acupuncture combined with vitamin B12 can reduce the risk of incomplete recovery compared with acupuncture alone in our meta-analysis. Because of study bias and methodological limitations, this conclusion is uncertain and the clinical application of acupuncture combined with vitamin B12 requires further exploration.

Aqueous extract of Gleditsia sinensis Lam. fruits improves serum and liver lipid profiles and attenuates atherosclerosis in rabbits fed a high-fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Gleditsia sinensis Lam. has been used in the traditional Chinese medicine as a chief ingredient of many polyherbal formulations for the treatment of obesity and thrombosis. AIM OF THE STUDY: To evaluate the effects of Gleditsia sinensis Lam. fruit aqueous extract (GAE) on hyperlipidemia and atherosclerosis in Japanese white rabbits on a high fat diet. MATERIALS AND METHODS: Rabbits were divided into four groups: the normal control with a normal diet, and high-fat diet-fed model group and GAE-treated groups supplemented with GAE (6 or 12 mg/kg/day, p.o.), respectively. The groups fed high-fat diets were given i.v. with bovine serum albumin (BSA) on the 4th week to induce atherosclerosis. The serum lipid profile, including triglycerides (TG), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), was determined on the 0th, 4th, 8th and 14th week, respectively. And the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) were measured simultaneously. At the end of the experiment, the rabbits were sacrificed, and the atherosclerotic plaques as well as the histopathological changes of aorta and liver were assessed by oil-red or HE staining, respectively, and the aorta and liver lipid profiles were also assayed. RESULTS: Results showed that the prophylactic treatment with GAE could significantly decrease the lipid levels of serum, aorta and liver, attenuate aortic atherosclerosis and improve aortic remodeling without the significant liver and muscle toxicity. CONCLUSION: The present findings suggest that GAE can effectively attenuate the atherosclerotic at least through anti-hyperlipidemic activity and thus has the therapeutic potential in treating hyperlipidemia-related cardiovascular diseases.

Saponins isolated from the root of Panax notoginseng showed significant anti-diabetic effects in KK-Ay mice.

Panax notoginseng, a well-known and commonly used traditional Chinese herb, has been used in China for six hundred years. Panax notoginseng saponins (PNS) were extracted from the root of the plant. This is the first study on anti-hyperglycemic and anti-obese effects of PNS in genetic model mice. Additionally, the preventive effect on diabetic nephropathy was investigated. Animals received intraperitoneal injections of PNS 50 or 200 mg/kg daily. On day 12, 22 and 30, PNS-treated groups had significantly lower fasting blood glucose levels and smaller body weight incremental percentage. After a 12-day treatment, glucose tolerance of PNS groups were significantly improved; these indices in PNS-treated mice exhibited a dose-dependent improvement. Furthermore, on day 30, the serum insulin resistance index and triglyceride levels of PNS-treated groups decreased significantly, and the development of the mice glomerular lesions was prevented significantly. The results in this present paper indicate that PNS possesses anti-diabetes and anti-obese activities and may prove to be of clinical importance in improving the management of type 2 diabetes.