Investigation of polysaccharide from Radix Aconiti Lateralis Preparata (Fuzi) cardio protective effect on doxorubicin-induced chronic cardiotoxicity.

OBJECTIVES: Doxorubicin (DOX) is a chemotherapy drug for treating malignant tumours. However, its cardiotoxicity has limited its clinical application. The Radix Aconiti Lateralis Preparata, also known as Fuzi, has been used for treating heart failure. Nevertheless, there is still a deficiency of claeity as to whether the Fuzi polysaccharide (FPS) may prevent the side effects of DOX. METHODS: Mice were intraperitoneally administered DOX (15 mg/kg) to establish a mouse model of DOX-induced chronic cardiotoxicity (DICC). The mice were then administered different doses of FPS or enalapril intragastrically. KEY FINDINGS: In the DOX group, the activity of CK-MB and LDH and the content of NT-proBNP in serum of mice were increased. Myocardial infiltration of inflammatory cells and cytoplasmic vacuolation occurred. Levels of NLRP3, ASC, Caspase-1, IL-1ß, IL-18, IL-6, and Bax increased, whereas levels of Bcl-2, STAT3, and p-STAT3 decreased. After administering FPS (100 mg/kg and 200 mg/kg), there were reductions in CK-MB activity and NT-proBNP levels. Cytoplasmic vacuolation, interstitial infiltration of blood, and infiltration of inflammatory cells were alleviated. The changes in protein expression mentioned above were reversed. CONCLUSIONS: FPS can protect heart function and structure in DICC mice by inhibiting NLRP3 inflammasome-mediated pyroptosis and IL-6/STAT3 pathway-induced apoptosis.

Galangin: A food-derived flavonoid with therapeutic potential against a wide spectrum of diseases.

Galangin is an important flavonoid with natural activity, that is abundant in galangal and propolis. Currently, various biological activities of galangin have been disclosed, including anti-inflammation, antibacterial effect, anti-oxidative stress and aging, anti-fibrosis, and antihypertensive effect. Based on the above bioactivities, more and more attention has been paid to the role of galangin in neurodegenerative diseases, rheumatoid arthritis, osteoarthritis, osteoporosis, skin diseases, and cancer. In this paper, the natural sources, pharmacokinetics, bioactivities, and therapeutic potential of galangin against various diseases were systematically reviewed by collecting and summarizing relevant literature. In addition, the molecular mechanism and new preparation of galangin in the treatment of related diseases are also discussed, to broaden the application prospect and provide reference for its clinical application. Furthermore, it should be noted that current toxicity and clinical studies of galangin are insufficient, and more evidence is needed to support its possibility as a functional food.

Bioactive compounds and mechanism of Xianglian pill in the treatment of gastric cancer: Network pharmacology analysis and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastric cancer (GC) affects people's quality of life because of its high incidence rate and mortality. The Xianglian Pill (XLP) is a traditional Chinese medicine (TCM) prescription used to treat gastrointestinal (GI） diseases. Its anti-tumor effect has been found in recent years, but it's bioactive compounds and mechanism of action in treating GC are remain unknown. AIM OF THE STUDY: This study reveals the bioactive compounds and mechanisms of XLP in the treatment of GC through network pharmacology analysis and experimental verification. MATERIALS AND METHODS: The main compounds in XLP were searched and the active compounds with anti-GC activity were selected. Compounds targets and GC- related targets were predicted, and common targets were obtained. Subsequently, a protein-protein interaction (PPI) network of common targets is constructed, while GO and KEGG enrichment analyses were performed on common targets. Finally, the anti-GC effects of active compounds in XLP were verified in GC cell lines MGC-803 and HGC-27 by wound healing assay, cell cycle assay, cell apoptosis assay and western blotting (WB) assay. RESULTS: A total of 33 active compounds of XLP were obtained. MTT assay showed that dehydrocostus lactone (DHL) and berberrubine (BRB) had lower IC50 value in GC cells HGC-27 and MGC-803, and has a less inhibitory effect on normal gastric epithelial cells. Further, 73 common targets were obtained after the total target of DHL and BRB intersected with GC. Among them, CASP3, AKT1, SRC, STAT3,and CASP9 were the most associated genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vitro experiment revealed that DHL and BRB inhibited GC cell viability via inducing cell cycle arrest at G2/M phase, and promoting cell apoptosis by up-regulating the caspase3 expression and down-regulating the expression of Bcl2/Bax. CONCLUSIONS: DHL and BRB are the two main anti-GC active compounds in XLP, and their mechanism is mainly to inhibit cell cycle and promote cell apoptosis.

The antibacterial activity of berberine against Cutibacterium acnes: its therapeutic potential in inflammatory acne.

Cutibacterium acnes (C. acnes) is a major pathogen implicated in the evolution of acne inflammation. Inhibition of C. acnes-induced inflammation is a prospective acne therapy strategy. Berberine (BBR), a safe and effective natural ingredient, has been proven to exhibit powerful antimicrobial and anti-inflammatory properties. However, the antimicrobial effect of BBR against C. acnes and its role in C. acnes-mediated inflammatory acne have not been explored. The objective of this investigation was to assess the antibacterial activity of BBR against C. acnes and its inhibitory effect on the inflammatory response. The results of in vitro experiments showed that BBR exhibited significant inhibition zones against four C. acnes strains, with the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in the range of 6.25-12.5 µg/mL and 12.5-25 µg/mL, respectively. On the bacterial growth curve, the BBR-treated C. acnes exhibited obvious growth inhibition. Transmission electron microscopy (TEM) images indicated that BBR treatment resulted in significant morphological changes in C. acnes. High-content imaging analysis further confirmed that BBR could effectively inhibit the proliferation of C. acnes. The disruption of cell wall and cell membrane structure by BBR treatment was preliminary confirmed according to the leakage of cellular contents such as potassium (K+), magnesium (Mg2+), and alkaline phosphatase (AKP). Furthermore, we found that BBR could reduce the transcript levels of genes associated with peptidoglycan synthesis (murC, murD, mraY, and murG). Meanwhile, we investigated the modulatory ability of BBR on C. acnes-induced skin inflammation in mice. The results showed that BBR effectively reduced the number of C. acnes colonized in mice's ears, thereby alleviating ear swelling and erythema and significantly decreasing ear thickness and weight. In addition, BBR significantly decreased the levels of pro-inflammatory cytokines IL-6, IL-1ß, and TNF-α in auricular tissues. These results suggest that BBR has the potential to treat inflammatory acne induced by C. acnes.

Rhein activated Fas-induced apoptosis pathway causing cardiotoxicity in vitro and in vivo.

Rhein, one of the main active components of rhubarb (Dahuang) and Polygonum multiflorum (Heshouwu), has a wide range of effective pharmacological effects. Recently, increasing studies have focused on its potential hepatorenal toxicity, but the cardiotoxicity is unknown. In this study, we found that the IC50 of rhein to H9c2 cells at 24 h and 48 h were 94.5 and 45.9µmol/L, respectively, with positive correlation of dose-toxicity and time-toxicity. After the treatment of rhein (106, 124 and 132µmol/L), the number of H9c2 cells decreased significantly, and the morphology of H9c2 cells showed atrophy, round shape and wall detachment. Moreover, the proportion of apoptotic cells in H9c2 cells treated with rhein was significantly increased in a dose-dependent manner. And rhein induced S phase arrest of H9c2 cells and inhibited cell proliferation. Rhein up-regulated ROS, LDH levels and low MMP but down-regulated SOD content in H9c2 cells. Additionally, the results showed that the cardiac function LVEF and LVFS of rhein high-medium-low dose groups (350, 175, 87.5 mg/kg) were significantly reduced. And the contents of Ca2+, cTnT, CK and LDH in serum of KM mice were significantly up-regulated by rhein. Furthermore, western blot results suggested that rhein the above effects via promoting Fas-induced apoptosis pathway in vitro and in vivo. In general, rhein may cause cardiotoxicity via Fas-induced apoptosis pathway in vivo and in vitro, which provides reference for the safe use of medicinal plant containing rhein and its preparations.

Guang Chen Pi (the pericarp of Citrus reticulata Blanco's cultivars 'Chachi') inhibits macrophage-derived foam cell formation.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried pericarp of Citrus reticulata Blanco (CP) occupies an important position in the history of clinical applications of traditional Chinese medicine (TCM). In traditional use, CP is used to treat diseases related to the digestive, respiratory, and cardiovascular systems, as well as to regulate Qi and promote blood circulation throughout the body. In China, a special cultivar of CP named Guang Chen Pi (GCP) which is collected exclusively from Citrus reticulata Blanco's cultivars 'Chachi', is considered to be the best CP with high medicinal and dietary value. Modern pharmacology shows that CP has high effect on regulating metabolic disorders and cardiovascular systems diseases. Atherosclerosis (AS) is not only an inflammatory disease but also cardiovascular lipid metabolism disorder. Foam cells formation is the hallmark of AS. Several reports indicated that CP can mitigate the development of AS, but involved signaling pathway and its role in foam cell formation is unclear. Since the main components of GCP has protective effects in cardiovascular diseases, we evaluated its effect of inhibiting foam cell formation to support the traditional usage of GCP. AIM OF THE STUDY: The objective of this study aims to investigate the effects of GCP on suppressing RAW264.7 foam cell formation and anti-inflammatory in vitro. MATERIALS AND METHODS: To evaluate the anti-foam cell formation and anti-inflammatory activity of GCP, oxidized low-density lipoprotein (ox-LDL) induced RAW264.7 macrophages model was involved. Meantime, foam cell developing status was also closely monitored. RT-qPCR and Western blot were then applied to further investigate receptors in associated signaling pathways. RESULTS: GCP shown inhibitory effect on macrophage-derived foam cell formation in Oil Red O staining analysis, which was further confirmed by flow cytometry of Dil-ox-LDL staining and TG and TC analysis. The HDL-mediated cholesterol efflux was also promoted by GCP. Mechanistic studies showed that GCP significantly down-regulate SRA1 and CD36 protein expression, while significantly increasing the expression of PPARγ, LXRα, SRB1 and ABCG1. Also, GCP reduced ox-LDL-induced inflammatory factors level, and inhibited phosphorylation of p38 MAPK, ERK1/2, JNK1/2, NF-κB p65 and IKKα/ß. CONCLUSIONS: GCP exhibited anti-atherogenic ability by interfering RAW264.7 foam cell formation, through inhibiting lipid uptake and promoting HDL-mediated cholesterol. PPARγ-LXRα-ABCG1/SRB1 pathway and its anti-inflammatory effect may involve. This proposed anti-foam cell formation activity is expected to provide new insight on comprehensive utilization of GCP.

Network pharmacology study on the mechanism of the herb pair of prepared Rehmannia root-Chinese arborvitae kernel for anxiety disorders.

BACKGROUND: Although anxiety disorders are one of the most common mental illness in population, antianxiety drugs often only have single action targets, require long-term use, and are associated with many adverse reactions and dependencies. Professor Yan Zhaojun from Shandong Provincial Hospital of Traditional Chinese Medicine (TCM) has applied the modified Renshu Powder, a TCM formula, to treat anxiety disorders, with satisfactory outcomes. Here, we investigated the mechanism of action of two core herbs (prepared Rehmannia root and Chinese arborvitae kernel) in the Renshu Powder in the treatment of anxiety disorders by using network pharmacology approaches. METHODS: Candidate compounds of the herb pair of prepared Rehmannia root-Chinese arborvitae kernel were extracted via the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. The targets of action of the main compounds were collected using the SwissTargetPrediction database. Targets associated with anxiety disorders were retrieved from DisGeNET, Online Mendelian Inheritance in Man (OMIM), DrugBank, GeneCards, and Comparative Toxicogenomics Database (CTD) databases. The compound-target interaction network was constructed by Cytoscape 3.7.2 software, and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) platform. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses the data by using Metascape. RESULTS: The main active compounds of the herb pair included arachidonic acid, stigmasterol, and beta-sitosterol. The key targets included Nitric Oxide Synthase 3 (NOS3), Epidermal growth factor (EGF), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Caspase 3 (CASP3), Mitogen-Activated Protein Kinase 1 (MAPK1), Peroxisome proliferator-activated receptor gamma (PPARG), RELA Proto-Oncogene, NF-KB Subunit (RELA), Estrogen Receptor 1 (ESR1), Solute Carrier Family 6 Member 4 (SLC6A4), and Phosphatase and Tensin homolog deleted on chromosome 10 (PTEN). Anxiety disorder-related GO analysis mainly involved synaptic signaling, neurotransmitter receptor activity, and G protein-coupled neurotransmitter receptor activity. The KEGG pathways involved neuroactive ligand-receptor interaction, serotonergic synapse, PI3K/AKT/mTOR signaling pathway, and MAPK signaling pathway. CONCLUSIONS: The mechanism of action of the prepared Rehmannia root-Chinese arborvitae kernel in treating anxiety disorders involves multiple ingredients, multiple targets, and pathways.

Yindan Jiedu Granules, a Traditional Chinese Medicinal Formulation, as a Potential Treatment for Coronavirus Disease 2019.

Background: Yindan Jiedu Granules (YDJDG) have been newly prescribed as a Chinese herbal formula. This study aimed to compare the efficacy of YDJDG and lopinavir-ritonavir in the treatment of coronavirus disease 2019 (COVID-19). Methods: Overall, 131 patients with COVID-19 were included in this study. In addition to standard care, 60 of these patients received YDJDG (YDJDG group) and 71 received lopinavir-ritonavir (lopinavir-ritonavir group). Propensity score matching (PSM) was used to match the characteristics of individuals in the two groups, while the Kaplan-Meier method was used to compare the proportion recovery observed. Results: Cox analysis revealed that YDJDG and CD4 ≥ 660 cells/µL were independent predictive factors of proportion recovery. At baseline, disease types differed between the YDJDG and lopinavir-ritonavir treatment groups. Furthermore, no significant adverse effects or toxicities relevant to YDJDG were observed. The median recovery time was 21 days in the YDJDG group and 27 days in the lopinavir-ritonavir group. After PSM (1:1), 50 patient pairs, YDJDG vs. lopinavir-ritonavir, were analyzed. In the YDJDG group, the proportion of recovered patients was remarkably higher than that observed in the lopinavir-ritonavir group (p = 0.0013), especially for those presenting mild/moderate disease type and CD4 < 660 cells/µL. In the YDJDG group, the mean duration of fever and pulmonary exudative lesions was significantly shorter than that observed in the lopinavir-ritonavir group (p = 0.0180 and p = 0.0028, respectively). Conclusion: YDJDG reveals the potential to hasten the recovery period in COVID-19 patients with mild/moderate disease type or CD4 < 660 cells/µL by shortening the mean duration of fever and pulmonary exudative lesions.

[Multi-central randomized controlled investigation on the massage for supplementing qi and removing obstruction in the Governor Vessel for treatment of infantile diarrhea due to spleen deficiency].

OBJECTIVE: To make multi-central clinical evaluation of the massage for supplementing qi and removing obstruction in the Governor Vessel for treatment of infantile diarrhea due to spleen deficiency. METHODS: By using multi-central, randomized and controlled method, 275 cases were randomly divided into an observation group (n = 137) and a control group (n = 138). The observation group were treated by the massage for supplementing qi and removing obstruction in the Governor Vessel, and the control group by routine massage therapy in Tuina Science, a teaching material for college and school of TCM. After treatment for 7 days, their therapeutic effects were compared. RESULTS: The cured rate was 83.2% in the observation group and 69.6% in the control group with a signifi cant difference between the two groups (P < 0.05), the former being better than the latter. The mean cured time was (3.22 +/- 1.04) days in the observation group and (4.20 +/- 1.11) days in the control group with a significant difference between the two groups (P < 0.05), the former being shorter than the latter. CONCLUSION: The massage for supplementing qi and removing obstruction in the Governor Vessel has a definite therapeutic effect on infantile diarrhea due to spleen deficiency, with rapid effect.

Multi-central randomized controlled investigation on the massage for supplementing qi and removing obstruction in the Governor Vessel for treatment of infantile diarrhea due to spleen deficiency / 中国针灸

<p><b>OBJECTIVE</b>To make multi-central clinical evaluation of the massage for supplementing qi and removing obstruction in the Governor Vessel for treatment of infantile diarrhea due to spleen deficiency.</p><p><b>METHODS</b>By using multi-central, randomized and controlled method, 275 cases were randomly divided into an observation group (n = 137) and a control group (n = 138). The observation group were treated by the massage for supplementing qi and removing obstruction in the Governor Vessel, and the control group by routine massage therapy in Tuina Science, a teaching material for college and school of TCM. After treatment for 7 days, their therapeutic effects were compared.</p><p><b>RESULTS</b>The cured rate was 83.2% in the observation group and 69.6% in the control group with a signifi cant difference between the two groups (P < 0.05), the former being better than the latter. The mean cured time was (3.22 +/- 1.04) days in the observation group and (4.20 +/- 1.11) days in the control group with a significant difference between the two groups (P < 0.05), the former being shorter than the latter.</p><p><b>CONCLUSION</b>The massage for supplementing qi and removing obstruction in the Governor Vessel has a definite therapeutic effect on infantile diarrhea due to spleen deficiency, with rapid effect.</p>

[A multicenter randomized controlled clinical trial on blood glucose lowering effects of domestic Acarbose (capsule) in type 2 diabetic patients].

OBJECTIVE: To assess the efficacy, tolerability, and safety of the domestic Acarbose capsule (DAC, produced by Luzhou Baoguang Pharmaceutical Co. LTD) in treating patients with type 2 diabetes mellitus. METHODS: One hundred and seventy nine type 2 diabetic patients were randomly divided into DAC (group A, 89 patients) and Glucoby (group B, 90 patients) treatment groups. The trial consisted of a 2-4 weeks equilibrated period followed by an 8 week course of treatments. All of the patients were followed up at the 4th week and 8th week after the commencement of the treatments. One hundred and sixty five patients completed the trial, with 81 in group A and 84 in group B. RESULTS: At the 4th week of the treatments, an average reduction of 1.81 and 2.08 mmol/L of fasting blood glucose (FBG) was found in group A and group B, respectively (P > 0.05); and an average reduction of 5.43 and 5.09 mmol/ L of postprandial blood glucose (PBG) was found in group A and group B, respectively (P > 0.05). At the 8th week, an average reduction of 2.35 and 2.62 mmol/L FBG was found in group A and group B, respectively (P > 0.05); and an average of reduction of 5.93 and 5.98 mmol/L of PBG was found in group A and group B, respectively (P > 0.05); The mean HbA(1c) was lowered by 1.07% and 1.20% by DAC and Glucoby respectively (P > 0.05). The incidence rate of side effects in group A was 32.53%, less than that in group B (48.81%). Flatulence was the most common side effect. The clinical effects of both Glucoby and DAC were more significant at the 8th week than at the 4th week. CONCLUSION: DAC is as effective and safe as Glucobay for treating type 2 diabetic patients.

[Multi-central controlled study on three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen].

OBJECTIVE: To make multi-central clinical evaluation for three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen. METHODS: One hundred and sixty-six cases were randomly divided into a test group (n = 84) and a control group (n = 82). Multi-central, randomized and controlled methods were adopted. The test group were treated by the three-part massage therapy, i. e. acupoints at the head, abdomen and back were massaged, once each day; and the control group by oral administration of Guipi Pills [symbol: see text], 8 pills each time, thrice daily. The treatment was given for 15 consecutive days and then the therapeutic effects were observed. RESULTS: Sixty-seven cases were cured, 11 markedly effective, 3 effective, and 3 ineffective in the test group, and the corresponding figures were 10, 21, 29 and 22 in the control group with a very significant difference between the two groups (P< 0.001). The test group was superior to the control group in improvement for Pittsburgh Sleep Quality Index (PSQI), Sleepless Anxiety Scale (SAS) and Sleepless Depression Scale (SDS) (P < 0.001). CONCLUSION: The three-part massage therapy has definite therapeutic effect on insomnia of deficiency of both the heart and spleen with safety.

Multi-central controlled study on three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen / 中国针灸

<p><b>OBJECTIVE</b>To make multi-central clinical evaluation for three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen.</p><p><b>METHODS</b>One hundred and sixty-six cases were randomly divided into a test group (n = 84) and a control group (n = 82). Multi-central, randomized and controlled methods were adopted. The test group were treated by the three-part massage therapy, i. e. acupoints at the head, abdomen and back were massaged, once each day; and the control group by oral administration of Guipi Pills [symbol: see text], 8 pills each time, thrice daily. The treatment was given for 15 consecutive days and then the therapeutic effects were observed.</p><p><b>RESULTS</b>Sixty-seven cases were cured, 11 markedly effective, 3 effective, and 3 ineffective in the test group, and the corresponding figures were 10, 21, 29 and 22 in the control group with a very significant difference between the two groups (P< 0.001). The test group was superior to the control group in improvement for Pittsburgh Sleep Quality Index (PSQI), Sleepless Anxiety Scale (SAS) and Sleepless Depression Scale (SDS) (P < 0.001).</p><p><b>CONCLUSION</b>The three-part massage therapy has definite therapeutic effect on insomnia of deficiency of both the heart and spleen with safety.</p>

[Study on treatment of multi-drug resistant falciparum malaria by using a combination of dihydroartemisinin and pyronaridine].

OBJECTIVE: To provide a combined medication scheme for the treatment of multi-drug resistant falciparum malaria. METHODS: Combined administration of dihydroartemisinin and pyronaridine was given to the 32 cases of falciparum malaria cases with multi-drug resistance. The indices for evaluation on day 14, 21, and 28 after treatment included the mean fever subsidence time, mean asexual form clearance time, mean recrudescence time of asexual form and recrudescence rate, proportion of gametocyte carriers, mean density of gametocytes and its mean clearance time, cure rate and rate of side-effects. A double blind clinical test was performed with standard schemes of dihydroartemisinin (20 cases) and pyronaridine (25 cases) as control. RESULTS: The mean fever subsidence time of treated patients by dihydroartemisinin/pyronaridine combination, dihydroartemisinin and pyronaridine was 35.7 +/- 24.7 h, 52.6 +/- 38.9 h and 35.8 +/- 16.5 h respectively, showing a significant difference between the combination group and dihydroartemisinin groups (P < 0.01). The mean asexual form clearance time was 23.8 +/- 10.1 h, 22.9 +/- 6.5 h and 49.4 +/- 20.3 h respectively, showing significantly faster in the combination group than the pyronaridine group (P < 0.01). The recrudescence rate was 0, 4.2% and 0 respectively. The proportion of gametocyte carriers was 20.0%, 16.7% and 60.9% respectively, with a significantly higher rate in the group of pyronaridine than the group of combination (P < 0.01). CONCLUSION: The combination of dihydroartemsinin and pyronaridine is an ideal medication scheme for the treatment of falciparum malaria cases with multi-drug resistance.