The latest medical research on Chinese Medical Practitioner

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Traditional Chinese Medicine Fufang-Zhenzhu-Tiaozhi capsule prevents renal injury in diabetic minipigs with coronary heart disease.

Chinese Medicine

Renal injury is one of the common microvascular complications of diabetes, known as diabetic kidney disease (DKD) seriously threatening human health. Previous research has reported that the Chinese Medicine Fufang-Zhenzhu-Tiaozhi (FTZ) capsule protected myocardia from injury in diabetic minipigs with coronary heart disease (DM-CHD). And we found significant renal injury in the minipigs. Therefore, we further investigated whether FTZ prevents renal injury of DM-CHD minipig and H2O2-induced oxidative injury of HK-2 cells.

DM-CHD model was established by streptozotocin injection, high fat/high-sucrose/high-cholesterol diet combined with balloon injury in the coronary artery. Blood lipid profile, fasting blood glucose (FBG), and SOD were measured with kits. The levels of blood urea nitrogen (BUN), serum creatinine (Scr), urine trace albumin (UALB), urine creatinine (UCR) (calculate UACR), cystatin (Cys-C), and β-microglobulin (β-MG) were measured by ELISA kits to evaluate renal function. TUNEL assay was performed to observe the apoptosis. qPCR was used to detect the mRNA expression levels of HO-1, NQO1, and SOD in kidney tissue. The protein expressions of Nrf2, HO-1, NQO1, Bax, Bcl-2, and Caspase 3 in the kidney tissue and HK-2 cells were detected by western blot. Meanwhile, HK-2 cells were induced by H2O2 to establish an oxidative stress injury model to verify the protective effect and mechanisms of FTZ.

In DM-CHD minipigs, blood lipid profile and FBG were elevated significantly, and the renal function was decreased with the increase of BUN, Scr, UACR, Cys-c, and β-MG. A large number of inflammatory and apoptotic cells in the kidney were observed accompanied with lower levels of SOD, Bcl-2, Nrf2, HO-1, and NQO1, but high levels of Bax and Cleaved-caspase 3. FTZ alleviated glucose-lipid metabolic disorders and the pathological morphology of the kidney. The renal function was improved and the apoptotic cells were reduced by FTZ administration. FTZ could also enhance the levels of SOD, Nrf2, HO-1, and NQO1 proteins to promote antioxidant effect, down-regulate the expression of Bax and Caspase3, as well as up-regulate the expression of Bcl-2 to inhibit cell apoptosis in the kidney tissue and HK-2 cells.

We concluded that FTZ prevents renal injury of DM-CHD through activating anti-oxidative capacity to reduce apoptosis and inhibiting inflammation, which may be a new candidate for DKD treatment.

Flavonoid-Rich Extract of Oldenlandia diffusa (Willd.) Roxb. Inhibits Gastric Cancer by Activation of Caspase-Dependent Mitochondrial Apoptosis.

Chinese Journal of Cancer

To evaluate the apoptosis and cycle arrest effects of Oldenlandia diffusa flavonoids on human gastric cancer cells, determine the action mechanisms in association with the mitochondrial dependent signal transduction pathway that controls production of reactive oxygen species (ROS), and evaluate the pharmacodynamics of a mouse xenotransplantation model to provide a reference for the use of flavonoids in prevention and treatment of gastric cancer.

Flavonoids were extracted by an enzymatic-ultrasonic assisted method and purified with D-101 resin. Bioactive components were characterized by high-performance liquid chromatography. Cell lines MKN-45, AGS, and GES-1 were treated with different concentrations of flavonoids (64, 96, 128, 160 µg/mL). The effect of flavonoids on cell viability was evaluated by MTT method, and cell nuclear morphology was observed by Hoechst staining. The apoptosis rate and cell cycle phases were measured by flow cytometry, the production of ROS was detected by laser confocal microscope, the mitochondrial membrane potential (MMP) were observed by fluorescence microscope, and the expression of apoptotic proteins related to activation of mitochondrial pathway were measured by immunoblotting. MKN-45 cells were transplanted into BALB/c nude mice to establish a xenograft tumor model. Hematoxylin and eosin staining was used to reveal the subcutaneous tumor tissue. The tumor volume and tumor weight were measured, the expression levels of proliferation markers proliferating cell nuclear antigen (PCNA) and Ki-67 were detected by immunohistochemistry, and the expression levels of CA72-4 were measured by enzyme linked immunosorbent assay.

Oldenlandia diffusa flavonoids inhibited proliferation of MKN-45 and AGS human gastric cancer cells, arrested the cell cycle in G1/S phase, induced accumulation of ROS in the process of apoptosis, and altered MMP. In addition, flavonoids increased Apaf-1, Cleaved-Caspase-3, and Bax, and decreased Cyclin A, Cdk2, Bcl-2, Pro-Caspase-9, and Mitochondrial Cytochrome C (P<0.05). The MKN-45 cell mouse xenotransplantation model further clarified the growth inhibitory effect of flavonoids towards tumors. The expression levels of PCNA and Ki-67 decreased in each flavonoid dose group, the expression level of CA72-4 decreased (P<0.05).

Flavonoids derived from Oldenlandia diffusa can inhibit proliferation and induce apoptosis of human gastric cancer cells by activating the mitochondrial controlled signal transduction pathway.

Discussion on Collection of Clinical Questions in International Clinical Practice Guidelines of Acupuncture-Moxibustion.

Chinese Journal of Cancer

The clinical questions of acupuncture-moxibustion (Acup-Mox) guidelines are complicated, including not only the curative effect of Acup-Mox interve...

Zhizhu Decoction Alleviates Intestinal Barrier Damage via Regulating SIRT1/FoxO1 Signaling Pathway in Slow Transit Constipation Model Mice.

Chinese Journal of Cancer

To explore the possible effects and mechanism of Zhizhu Decoction (ZZD) on the pathophysiology of slow transit constipation (STC).

A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table, including control, STC model (model), positive control, and low-, medium- and high-doses ZZD treatment groups (5, 10, 20 g/kg, namely L, M-, and H-ZZD, respectively), 9 mice in each group. Following 2-week treatment, intestinal transport rate (ITR) and fecal water content were determined, and blood and colon tissue samples were collected. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells. To determine intestinal permeability, serum levels of lipopolysaccharide (LPS), low-density lipoprotein (LDL) and mannose were measured using enzyme-linked immunosorbent assay (ELISA). Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1 (ZO-1), claudin-1, occludin and recombinant mucin 2 (MUC2). The mRNA expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4, IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction. Colon indexes of oxidative stress were measured by ELISA, and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1 (SIRT1/FoxO1) antioxidant signaling pathway were detected by Western blot.

Compared with the model group, ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups (P<0.01). Additionally, ZZD treatment notably increased the thickness of mucosal and muscular tissue, elevated the number of goblet cells in the colon of STC mice, reduced the secretion levels of LPS, LDL and mannose, and upregulated ZO-1, claudin-1, occludin and MUC2 expressions in the colon in a dose-dependent manner, compared with the model group (P<0.05 or P<0.01). In addition, ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway (P<0.05 or P<0.01).

ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon.

Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation.

Chinese Journal of Cancer

To investigate the mechanism of the effect of Astragalus membranaceus (A. membranaceus) on lung adenocarcinoma at the molecular level to elucidate the specific targets according to the network pharmacology approach.

The active components of A. membranaceus and their potential targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database. Lung adenocarcinoma-associated genes were acquired based on GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGKB, and Therapeutic Targets databases. The PI3K/AKT signaling pathway-related genes were obtained using Reactome portal. Networks of "ingredient-target" and "ingredient-target-pathway-disease" were constructed using the Cytoscape3.6.0 software. The relationships among targets were analyzed according protein-protein interaction (PPI) network. Finally, molecular docking was applied to construct the binding conformation between active ingredients and core targets. Cell counting kit 8 (CCK8) and Western blot assays were performed to determine the mechanism of the key ingredient of A. membranaceus.

A total of 20 active components and their 329 targets, and 7,501 lung adenocarcinoma-related genes and 130 PI3K/AKT signaling pathway-related genes were obtained. According to Venn diagram and PPI network analysis, 2 mainly active ingredients, including kaempferol and quercetin, and 6 core targets, including TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR, were identified. The two important active ingredients of A. membranaceus, kaempferol and quercetin, exert the therapeutic effect in lung adenocarcinoma partly by acting on the 6 core targets (TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR) of PI3K/AKT signaling pathway. Expressions of potential targets in lung adenocarcinoma and normal samples were analyzed by using UALCAN portal and found that ERBB2 was overexpressed in lung adenocarcinoma tissues and upregulation of it correlated with clinicopathological characteristics. Finally, quercetin repressed viabilities of lung adenocarcinoma cells by targeting ERBB2 on PI3K/AKT signaling confirmed by CCK8 and Western blot.

Our finding unraveled that an active ingredient of A. membranaceus, quercetin, significantly inhibited the lung adenocarcinoma cells proliferation by repressing ERBB2 level and inactivating the PI3K/AKT signaling pathway.

Mechanism Study on Chinese Medicine in Treatment of Nodular Goiter.

Chinese Journal of Cancer

Nodular goiter has become increasingly prevalent in recent years. Clinically, there has been a burgeoning interest in nodular goiter due to the ris...

Quantification of prevalence, clinical characteristics, co-existence, and geographic variations of traditional Chinese medicine diagnostic patterns via latent tree analysis-based differentiation rules among functional dyspepsia patients.

Chinese Medicine

Traditional Chinese Medicine (TCM) treatment strategies are guided by pattern differentiation, as documented in the eleventh edition of the International Classification of Diseases (ICD). However, no standards for pattern differentiation are proposed to ensure inter-rater agreement. Without standardisation, research on associations between TCM diagnostic patterns, clinical features, and geographical characteristics is also not feasible. This diagnostic cross-sectional study aimed to (i) establish the pattern differentiation rules of functional dyspepsia (FD) using latent tree analysis (LTA); (ii) compare the prevalence of diagnostic patterns in Hong Kong and Hunan; (iii) discover the co-existence of diagnostic patterns; and (iv) reveal the associations between diagnostic patterns and FD common comorbidities.

A total of 250 and 150 participants with FD consecutively sampled in Hong Kong and Hunan, respectively, completed a questionnaire on TCM clinical features. LTA was performed to reveal TCM diagnostic patterns of FD and derive relevant pattern differentiation rules. Multivariate regression analyses were performed to quantify correlations between different diagnostic patterns and between diagnostic patterns and clinical and geographical variables.

At least one TCM diagnostic pattern was differentiated in 70.7%, 73.6%, and 64.0% of the participants in the overall (n = 400), Hong Kong (n = 250), and Hunan (n = 150) samples, respectively, using the eight pattern differentiation rules derived. 52.7% to 59.6% of the participants were diagnosed with two or more diagnostic patterns. Cold-heat complex (59.8%) and spleen-stomach dampness-heat (77.1%) were the most prevalent diagnostic patterns in Hong Kong and Hunan, respectively. Spleen-stomach deficiency cold was highly likely to co-exist with spleen-stomach qi deficiency (adjusted odds ratio (AOR): 53.23; 95% confidence interval (CI): 21.77 to 130.16). Participants with severe anxiety tended to have liver qi invading the stomach (AOR: 1.20; 95% CI: 1.08 to 1.33).

Future updates of the ICD, textbooks, and guidelines should emphasise the importance of clinical and geographical variations in TCM diagnosis. Location-specific pattern differentiation rules should be derived from local data using LTA. In future, patients' pattern differentiation results, local prevalence of TCM diagnostic patterns, and corresponding TCM treatment choices should be accessible to practitioners on online clinical decision support systems to streamline service delivery.

In Silico Prediction of Andrographolide Dosage Regimens for COVID-19 Treatment.

American Journal of

Andrographolide (APE) has been used for COVID-19 treatment in various clinical settings in South-East Asia due to its benefits on reduction of vira...

Propolis: An update on its chemistry and pharmacological applications.

Chinese Medicine

Propolis, a resinous substance produced by honeybees from various plant sources, has been used for thousands of years in traditional medicine for s...

Effects of Chinese medicine for COVID-19 rehabilitation: a multicenter observational study.

Chinese Medicine

This study aimed to evaluate the effects of Chinese Medicine (CM) on the health condition of the post-COVID-19 patients, particularly with the CM Syndrome diagnosis and Body Constitutions (BC), as well as related clinical characteristics.

150 participants who had COVID-19 and discharged from Hong Kong public hospitals were recruited. They were provided with three to six months of CM treatments, during which assessments were made per month and at follow-up on their CM syndromes, BC, lung functions, and other medical conditions. This study was divided into two parts: (1) Retrospective survey: medical history of participants during COVID-19 hospitalization was collected during the baseline visit; (2) Prospective observation and assessments: clinical symptoms, lung functions, and BC status were evaluated in participants receiving CM treatment based on syndrome differentiation and clinical symptoms.

The median hospitalization period was 16 days. Symptoms were presented in 145 (96.6%) patients at the day they were diagnosed with COVID-19. Fever, fatigue, and dry cough were the most common symptoms, exhibiting in 59.3% (89 of 150), 55.3% (83 of 150), and 46% (70 of 150) participants, respectively. Among the 150 post-COVID patients, majority (71.3%) were of the two particular post-COVID CM Syndromes (Qi Deficiency of Lung and Spleen, and Qi and Yin Deficiency). Upon CM treatment, there was an observable increase in participants reaching a balanced BC (i.e. healthy body conditions). The increase was observed to be more prominent in those without the particular CM Syndromes compared to those with the CM Syndromes. Main clinical symptoms in participants with the CM Syndromes decreased upon CM treatment. Occurrence of fatigue also dropped after CM treatment though not all accompanied clinical symptoms were resolved fully. Further to the improvement in terms of CM assessments, lung functions of the participants were found to show improvement after treatment. Both the performance in 6MWT and scores in the LFQ improved upon CM treatments (P < 0.05).

This study provided evidence for individualized CM treatment on COVID-19 rehabilitation concerning the clinical symptoms improvements, lung functions improvement, and achieving a balanced BC. It is believed that CM may be a key to further promote rehabilitation and resolution of residual symptoms. Long-term large scale follow-up studies on sub-categorising post-COVID patients according to different CM syndromes would be required to further elucidate treatment of persistent symptoms that may be associated with long-COVID.

Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study.

Chinese Journal of Cancer

To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism.

Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines.

A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis.

Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

Shenmai Injection Attenuates Myocardial Ischemia/Reperfusion Injury by Targeting Nrf2/GPX4 Signalling-Mediated Ferroptosis.

Chinese Journal of Cancer

To examine the effect of Shenmai Injection (SMJ) on ferroptosis during myocardial ischemia reperfusion (I/R) injury in rats and the underlying mechanism.

A total of 120 SPF-grade adult male SD rats, weighing 220-250 g were randomly divided into different groups according to a random number table. Myocardial I/R model was established by occluding the left anterior descending artery for 30 min followed by 120 min of reperfusion. SMJ was injected intraperitoneally at the onset of 120 min of reperfusion, and erastin (an agonist of ferroptosis), ferrostatin-1 (Fer-1, an inhibitor of ferroptosis) and ML385 (an inhibitor of nuclear factor erythroid-2 related factor 2 (Nrf2)) were administered intraperitoneally separately 30 min before myocardial ischemia as different pretreatments. Cardiac function before ischemia, after ischemia and after reperfusion was analysed. Pathological changes in the myocardium and the ultrastructure of cardiomyocytes were observed, and the myocardial infarction area was measured. Additionally, the concentration of Fe2+ in heart tissues and the levels of creatine kinase-MB (CK-MB), troponin I (cTnl), malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were measured using assay kits, and the expressions of Nrf2, glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were examined by Western blot.

Compared with the sham group, I/R significantly injured heart tissues, as evidenced by the disordered, ruptured and oedematous myocardial fibres; the increases in infarct size, serum CK-MB, cTnI and MDA levels, and myocardial Fe2+ concentrations; and the decreases in SOD activity (P<0.05). These results were accompanied by ultrastructural alterations to the mitochondria, increased expression of ACSL4 and inhibited the activation of Nrf2/GPX4 signalling (P<0.05). Compared with I/R group, pretreatment with 9 mL/kg SMJ and 2 mg/kg Fer-1 significantly reduced myocardial I/R injury, Fe2+ concentrations and ACSL4 expression and attenuated mitochondrial impairment, while 14 mg/kg erastin exacerbated myocardial I/R injury (P<0.05). In addition, cardioprotection provided by 9 mL/kg SMJ was completely reversed by ML385, as evidenced by the increased myocardial infarct size, CK-MB, cTnI, MDA and Fe2+ concentrations, and the decreased SOD activity (P<0.05).

Ferroptosis is involved in myocardial I/R injury. Pretreatment with SMJ alleviated myocardial I/R injury by activating Nrf2/GPX4 signalling-mediated ferroptosis, thereby providing a strategy for the prevention and treatment of ischemic heart diseases.