Effects of Chinese herbal medicine in patients with benign prostatic hyperplasia: A nationwide cohort study in Taiwan.

OBJECTIVES: Benign prostatic hyperplasia affects elderly males, with progression presenting the risk of urinary complications and eventual surgical intervention. We aimed to evaluate the effects of Chinese herbal medicine in patients with benign prostatic hyperplasia. METHODS: This retrospective cohort study analyzed claims data in Taiwan's National Health Insurance Research Database from 2001 to 2013. A total of 4142 patients newly diagnosed as benign prostatic hyperplasia were enrolled and divided into cohorts of Chinese herbal medicine users and nonusers by performing 1:1 propensity score matching. The risk of benign prostatic hyperplasia-related complications was assessed by the Cox proportional hazard model. The cumulative incidence of benign prostatic hyperplasia-related surgeries was assessed by Kaplan-Meier method. RESULTS: During the study period, the risk of benign prostatic hyperplasia-related complications was lower in the Chinese herbal medicine cohort than non-Chinese herbal medicine cohort with an adjusted hazard ratio of 0.82 (95% confidence interval 0.73-0.92) after controlling for multiple variables. Subgroup analysis revealed that Chinese herbal medicine users had a significantly lower risk of urinary tract infection (adjusted hazard ratio 0.67, 95% confidence interval 0.50-0.89) and urinary retention (adjusted hazard ratio 0.83, 95% confidence interval 0.72-0.97). In addition, Chinese herbal medicine users also had a lower incidence rate of benign prostatic hyperplasia-related surgery (32.14 vs 40.20, adjusted hazard ratio 0.74, 95% confidence interval 0.61-0.89) and a longer surgery-free interval than non-Chinese herbal medicine users (3.98 vs 3.00 mean person-year, P < 0.001). Data revealed Salviae miltiorrhizae and Ji-Sheng-Shen-Qi-Wan as the most commonly prescribed Chinese herbal medicine by traditional Chinese medicine practitioners. CONCLUSIONS: Our study demonstrated that Chinese herbal medicine might have effects in the benign prostatic hyperplasia-related complications and surgeries in patients with benign prostatic hyperplasia.

D-galactose-induced toxicity associated senescence mitigated by alpinate oxyphyllae fructus fortified adipose-derived mesenchymal stem cells.

This study addresses the effect of D-galactose-induced toxicity associated senescence mitigated by alpinate oxyphyllae fructus (AOF; Alpinia oxyphylla Miq) extracts fortified with adipose-derived mesenchymal stem cells (ADMSCs) in rats. Male 18 week-old Wistar Kyoto (WKY) rats were used in this study. We analyzed cardiac fibrosis by Masson's trichrome staining. The tissue sections were dyed using hematoxylin and eosin (H&E). Tissue sections were stained for the restoration of Nrf2 expression in treatment groups by immunohistochemistry. Immunohistochemistry and western blotting analysis showed that AOF with ADMSCs could significantly reduce aging-induced oxidative stress in D-galactose-induced aging rat hearts by inducing Nrf2 pathway. Reduction in ROS resulted in the suppression of inflammatory signals (p-NF-κB and IL-6). Histopathological studies were showed an increased interstitium and collagen accumulation in aging-induced heart sections. However, AOF and ADMSCs treated hearts were recovered from cardiac remodeling. Furthermore, hypertrophy and fibrosis associated markers were also significantly reduced (P < .05) in treatment groups. We speculate that ADMSCs might activate certain paracrine factors, which could target the upstream activator of aging associated cardiac complications and AOF might provide homing for these stem cells.

Association between erectile dysfunction and fibromyalgia in male patients: A Taiwanese nationwide population-based cohort study.

OBJECTIVES: To investigate the association between erectile dysfunction and fibromyalgia, and to clarify related comorbidities and treatment modalities. METHODS: This retrospective cohort study was carried out using 1 million records in the National Health Insurance Research Database. From 2001 to 2012, a total of 53 678 male patients newly diagnosed with fibromyalgia were recruited as the fibromyalgia cohort, and the same number of the non-fibromyalgia cohort was enrolled and matched with propensity score with age, income, comorbidities, and prescribed medications. All records were followed up until the end of 2013. The Cox proportional hazards model was carried out to assess the risk of erectile dysfunction among fibromyalgia patients. RESULTS: The incidence rates of erectile dysfunction were 36.86 and 21.15 (per 10 000 person-years) in the fibromyalgia and non-fibromyalgia cohorts, respectively, and a significantly increased risk of erectile dysfunction in fibromyalgia patients was noted (adjusted hazard ratio 1.69, 95% confidence interval 1.55-1.85, P < 0.001). The Cox proportional hazards regression analysis showed increased risk of erectile dysfunction in the fibromyalgia cohort regardless of treatment prescriptions of tramadol, antidepressants, gabapentin and non-steroidal anti-inflammatory drugs. CONCLUSIONS: Fibromyalgia was found to be an independent risk factor for the incidence of erectile dysfunction.

Alpinia oxyphylla Miq extract ameliorates cardiac fibrosis associated with D-galactose induced aging in rats.

Cardiac fibrosis is a common pathophysiological process observed during chronic and stress-induced acceleration of cardiac aging. Fibrosis is a necessary process during wound healing and tissue repair. However, its deposition in organs would proceed to scarring and organ damage. Here Alpinate Oxyphyllae Fructus (AOF), a Chinese medicine extract was used to protect aging heart from collagen accumulation. About 8 weeks old, male SD rats were randomly divided into (i) Control, (ii) D-galactose induced aging (IA), (iii) IA + AOF 50 (AOF low, AL), (iv) IA + AOF 100 (AOF medium, AM), (v) IA + AOF 150 (AOF high, AH) mg/kg/day, AOF was administered orally. After 8 weeks rats were sacrificed and hearts were collected. Results showed collagen deposition and up-regulation of matrix metalloproteinases-MMP-2 and -9 in D-galactose-induced aging rats. Furthermore, western blotting and immunostaining were also confirmed the upregulation of TGF-ß1 mediated fibrosis in aging induced rats. However, collagen deposition and fibrosis were significantly decreased by AOF treatments (AM and AH). AOF treatments salvaged the cardiac fibrosis. Hence, AOF might be a potential therapeutic agent in the prevention of cardiac fibrosis associated with aging. The protective effects of AOF might have promising results in anti-aging treatments.

Naringenin attenuates hepatitis B virus X protein-induced hepatic steatosis.

BACKGROUND: Naringenin (Nar), a common dietary flavonoid abundantly present in fruits, vegetables, and Chinese herbs, is believed to possess strong anti-inflammatory properties and to modulate hepatic apolipoprotein and lipid synthesis. However, there are no reports describing Nar's effects on the hepatitis B virus protein X (HBx) -induced hepatic steatosis, and the detailed molecular mechanisms of the compound's effects are still unclear. METHODS: Nar was administered by oral gavage to HBx-transgenic mice from 4 to 6 weeks of age. Mice were sacrificed after 14 days of once-daily naringenin administration. Liver tissues and sera were collected for histopathology and biochemical analysis. RESULTS: Nar counteracted hepatic lipid accumulation and liver dysfunction in HBx-transgenic mice. In addition, Nar significantly decreased expression of adipogenic and lipogenic genes in mice, suggesting that the compound may have therapeutic effects in the early stages of HBx-mediated hepatic steatosis. These results indicated that naringenin inhibits HBx-induced expression of hepatic adipogenic and lipogenic genes through suppression of HBx-induced gene expression, including decreases in the transcriptional activity of SREBP1c, LXRα, and PPARγ in HBx-trangenic mice and HBx-transfected HepG2 cells. CONCLUSIONS: Results from this study suggested that Nar may serve as a therapeutic agent for preventing HBx-infected hepatic steatosis in humans.

Alpinia oxyphylla Miq. fruit extract activates IGFR-PI3K/Akt signaling to induce Schwann cell proliferation and sciatic nerve regeneration.

BACKGROUND: It is known that the medicinal herb Alpinia oxyphylla Miq. is widely used as a remedy for diarrhea as well as the symptoms accompanying hypertension and cerebrovascular disorders. Moreover, it has also been reported that Alpinia oxyphylla Miq. has beneficial effects on anti-senescence and neuro-protection. This study focuses on the molecular mechanisms by which the Alpinia oxyphylla Miq. fruits promote neuron regeneration. METHODS: A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with various doses of Alpinia oxyphylla Miq. fruits to assess their regenerative effect on damaged nerves. Further, we investigated the role of Alpinia oxyphylla Miq. fruits in RSC96 Schwann cell proliferation. RESULTS: Our current results showed that treatment with the extract of Alpinia oxyphylla Miq. fruits triggers the phosphorylated insulin-like growth factor-1 receptor- phosphatidylinositol 3-kinase/serine-threonine kinase pathway, and up-regulated the proliferating cell nuclear antigen in a dose-dependent manner. Cell cycle analysis on RSC96 Schwann cells showed that, after exposure to Alpinia oxyphylla Miq. fruit extract, the transition from the first gap phase to the synthesis phase occurs in 12-18 h. The expression of the cell cycle regulatory proteins cyclin D1, cyclin E and cyclin A increased in a dose-dependent manner. Transfection with a small interfering RNA blocked the expression of phosphatidylinositol 3-kinase and induced down-regulation both on the mRNA and protein levels, which resulted in a reduction of the expression of the survival factor B-cell lymphoma 2. CONCLUSION: We provide positive results that demonstrate that Alpinia oxyphylla Miq. fruits facilitate the survival and proliferation of RSC96 cells via insulin-like growth factor-1 signaling.

Anti-Apoptotic and Pro-Survival Effect of Alpinate Oxyphyllae Fructus (AOF) in a d-Galactose-Induced Aging Heart.

Aging, a natural biological/physiological phenomenon, is accelerated by reactive oxygen species (ROS) accumulation and identified by a progressive decrease in physiological function. Several studies have shown a positive relationship between aging and chronic heart failure (HF). Cardiac apoptosis was found in age-related diseases. We used a traditional Chinese medicine, Alpinate Oxyphyllae Fructus (AOF), to evaluate its effect on cardiac anti-apoptosis and pro-survival. Male eight-week-old Sprague-Dawley (SD) rats were segregated into five groups: normal control group (NC), d-Galactose-Induced aging group (Aging), and AOF of 50 (AL (AOF low)), 100 (AM (AOF medium)), 150 (AH (AOF high)) mg/kg/day. After eight weeks, hearts were measured by an Hematoxylin-Eosin (H&E) stain, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-assays and Western blotting. The experimental results show that the cardiomyocyte apoptotic pathway protein expression increased in the d-Galactose-Induced aging groups, with dose-dependent inhibition in the AOF treatment group (AL, AM, and AH). Moreover, the expression of the pro-survival p-Akt (protein kinase B (Akt)), Bcl-2 (B-cell lymphoma 2), anti-apoptotic protein (Bcl-xL) protein decreased significantly in the d-Galactose-induced aging group, with increased performance in the AOF treatment group with levels of p-IGFIR and p-PI3K (Phosphatidylinositol-3' kinase (PI3K)) to increase by dosage and compensatory performance. On the other hand, the protein of the Sirtuin 1 (SIRT1) pathway expression decreased in the aging groups and showed improvement in the AOF treatment group. Our results suggest that AOF strongly works against ROS-induced aging heart problems.

The Chinese medicine Sini-San inhibits HBx-induced migration and invasiveness of human hepatocellular carcinoma cells.

BACKGROUND: Sini-San (SNS) is a formulation of four Traditional Chinese Drugs that exhibits beneficial therapeutic effects in liver injury and hepatitis. However, there are no reports describing its effects on the hepatitis B X-protein (HBx)-induced invasion and metastasis in hepatoma cells, and the detailed molecular mechanisms of its actions are still unclear. METHODS: In this study, we investigated the mechanisms underlying SNS-mediated inhibition of HBx-induced cell invasion and the inhibition of secreted and cytosolic MMP-9 production, using gelatin zymography and Western blot analysis in a human hepatoma cell line (HepG2). Relative luciferase activity was assessed for MMP-9, NF-κB, or AP-1 reporter plasmid-transfected cells. RESULTS: SNS suppressed MMP-9 transcription by inhibiting activator protein (AP)-1 and nuclear factor-κ B (NF-κB) activity. SNS suppressed HBx-induced AP-1 activity through inhibition of phosphorylation in the extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways. SNS also suppressed HBx-induced inhibition of NF-κB nuclear translocation through IκB and suppressed HBx-induced activation of ERK/phosphatidylinositol 3-kinase/Akt upstream of NF-κB and AP-1. CONCLUSIONS: SNS suppresses the invasiveness and metastatic potential of hepatocellular carcinoma cells by inhibiting multiple signal transduction pathways.

Modifiable vascular risk factors contribute to stroke in 1080 NOTCH3 R544C carriers in Taiwan Biobank.

BACKGROUND AND AIM: Previous studies have suggested cardiovascular risk factors increase the risk of not only common sporadic stroke but also of stroke in patients with monogenic stroke disorders including CADASIL. We investigated the effects of the NOTCH3 Arg544Cys (R544C) variant and associated vascular risk factors on stroke in the Taiwanese population. METHODS: This study was conducted using data from the Taiwan Biobank, consisting of at least 130,000 Han Chinese participants. The genotype was derived from customized genome-wide arrays for 650,000 to 750,000 single-nucleotide polymorphisms (SNPs). Individuals with NOTCH3 R544C were subsequently matched with noncarriers based on the propensity score at a 1:10 ratio by demographic and cardiovascular risk factors. The odds ratio (OR) for stroke or other phenotypes in NOTCH3 R544C carriers and matched noncarriers was then calculated. Univariate and multivariate regression analyses were performed on cardiovascular risk factors in NOTCH3 R544C carriers with and without stroke. The polygenic risk score (PRS) model, adopted from the UK Biobank, was then applied to evaluate the role of NOTCH3 R544C in stroke. RESULTS: From the 114,282 participants with both genotype and questionnaire results, 1080 (0.95%) harbored the pathogenic NOTCH3 R544C variant. When compared to the matched controls (n = 10,800), the carriers presented with a history of stroke (OR: 2.52, 95% confidence interval (CI) (1.45, 4.37)), dementia (OR: 30.1, 95% CI (3.13, 289.43)), and sibling history of stroke (OR: 2.48, 95% CI (1.85, 3.34)) phenotypes. The risk of stroke increased with every 10-year increase in age (p = 0.006, Cochran-Mantel-Haenszel test). Among NOTCH3 R544C carriers, 16 (1.3%) of the 1080 carriers with a stroke history were older, male, and more likely to have hypertension, diabetes, dyslipidemia, and a family history of stroke. In the stepwise multivariate analysis, hypertension (OR: 11.28, 95% CI (3.54, 43.3)) and diabetes mellitus (OR: 4.10, 95% CI (1.31, 12.4)) were independently associated with stroke. Harboring the NOTCH3 R544C variant in the Taiwan Biobank is comparable with a 6.74 standard deviations increase in individual's polygenic risk score for stroke. CONCLUSION: While the NOTCH3 R544C variant alone increased the risk of stroke, modifiable vascular risk factors also played a role in the occurrence of stroke in Taiwanese community-dwelling individuals carrying the NOTCH3 variant.

Roles of conventional and complementary therapies in recurrent hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the fourth leading cause of cancer-related deaths in the world. HCC has a reported recurrence rate of 70%-80% after 5 years of follow-up. Controlling tumor recurrence is the most critical factor associated with HCC mortality. Conventional salvage therapies for recurrent HCC include re-hepatectomy or liver transplantation, transcatheter arterial chemoembolization, Y-90, target therapy, and immunotherapy; however, these conventional treatment modalities have yet to achieve consistently favorable outcomes. Meanwhile, previous studies have demonstrated that conventional therapies in combination with traditional Chinese medicine (TCM), acupuncture, moxibustion or dietary supplements could notably benefit patients with HCC recurrence by strengthening and augmenting the overall management strategy. However, systemic reviews related to the interactions between complementary therapies and conventional therapy in recurrent HCC are limited. In this review, we discuss the molecular mechanisms underlying the functions of complementary therapies for recurrent HCC, which include augmenting the local control to improve the congestion status of primary tumors and reducing multicentric tumor occurrence via inducing autophagy, apoptosis or cell cycle arrest. TCM and its derivatives may play important roles in helping to control HCC recurrence by inhibiting epithelial-mesenchymal transition, migration, invasion, and metastasis, inhibiting cancer stem cells, and ameliorating drug resistance.

LipoCol Forte capsules reduce the risk of liver cancer: A propensity score-matched, nationwide, population-based cohort study.

BACKGROUND: Liver cancer is among the top five most common cancers globally. Lipid-lowering drugs such as statins can lower the risk of liver cancer, but may also cause liver damage. LipoCol Forte capsules (LFC), a red yeast rice product, have demonstrated significant antihypercholesterolemic effects and a good safety profile in clinical studies. AIM: To evaluate whether LFC lowers the risk of liver cancer in adults in this propensity score-matched, nationwide, population-based cohort study. METHODS: We used data from Taiwan's National Health Insurance Research Database, which includes electronic medical records for up to 99.99% of Taiwan's population. LFC users and LFC non-users were matched 1:1 by propensity scores between January 2010 and December 2017. All had follow-up data for at least 1 year. Statistical analyses compared demographic distributions including sex, age, comorbidities, and prescribed medications. Cox regression analyses estimated adjusted hazard ratios (aHRs) after adjusting for potential confounders. RESULTS: We enrolled 33231 LFC users and 33231 non-LFC users (controls). No significant differences between the study cohorts were identified regarding comorbidities and medications [standardized mean difference (SMD) < 0.05]. At follow-up, the overall incidence of liver cancer was significantly lower in the LFC cohort compared with controls [aHR 0.91; 95% confidence interval (CI): 0.86-0.95; P < 0.001]. The risk of liver cancer was significantly reduced in both females (aHR 0.87; 95%CI: 0.8-0.94; P < 0.001) and males (aHR 0.93; 95%CI: 0.87-0.98; P < 0.01) in the LFC cohort compared with their counterparts in the non-LFC cohort. The antitumor protective effects applied to patients with comorbidities (including hypertension, ischemic stroke, diabetes mellitus, hyperlipidemia, hepatitis B infection and hepatitis C infection). Those using LFC for more than 84 drug days had a 0.64-fold lower risk of liver cancer compared with controls (P < 0.001). Compared with controls, the risk of developing liver cancer in the LFC cohort progressively decreased over time; the lowest incidence of liver cancer occurred in LFC users followed-up for more than 6 years (27.44 vs 31.49 per 1,000 person-years; aHR 0.75; 95%CI: 0.68-0.82; P < 0.001). CONCLUSION: This retrospective cohort study indicates that LFC has a significantly protective effect on lowering the risk of liver cancer, in a dose-dependent and time-dependent manner.

Integrated Chinese herbal medicine and Western medicine successfully resolves spontaneous subcutaneous emphysema and pneumomediastinum in a patient with severe COVID-19 in Taiwan: A case report.

CASE: Serious complications of severe coronavirus disease 2019 (COVID-19) include subcutaneous emphysema (SE) and pneumomediastinum, which are complicated to treat with conventional Western medicine. We report how combining Chinese herbal medicine (CHM) with Western medicine quickly resolved a patient's COVID-19-associated pulmonary complications, shortened hospital stay and improved quality of life. CLINICAL FEATURES AND OUTCOME: A 59-year-old male with a history of smoking and tumors was diagnosed with COVID-19 in May 2021. At hospitalization, his oxygen saturation (SpO2) was 80%, he had a continuous severe cough, rapid shallow breathing, spontaneous SE and pneumomediastinum. By Day 4 of hospitalization, his condition was worsening despite standard care, so CHM was added. After 3-5 days, his coughing had lessened and supplementary oxygen therapy was de-escalated. Nine days after starting CHM, the SE had completely resolved and the patient avoided intubation. His WHO OS 10-point Scale score had fallen from 6 to 3 points and the modified Medical Research Council Dyspnea Scale score from 4 to 2 points. He was hospitalized for 19 days. At 1 week post-discharge, the patient could handle most of his daily activities and experienced minor shortness of breath only when performing labor-intensive tasks. At 1 month, his work output was restored to pre-COVID-19 levels. CONCLUSION: CHM combined with standard Western medicine improved pulmonary function, respiratory rate, blood oxygen saturation and shortened the hospital stay of a patient with severe COVID-19 complicated by SE and pneumomediastinum.

Concurrent use of Chinese herbal medicine and anticoagulants may reduce major bleeding events.

BACKGROUND: This retrospective cohort study investigated the risk of major bleeding events during the concurrent use of Chinese herbal medicine (CHM) and anticoagulants in clinical practice. METHODS: A total of 4,470 patients receiving anticoagulant drugs were selected from Taiwan's National Health Insurance Research Database (NHIRD). Half (n = 2,235) were also using CHMs (CHM cohort); the other half were not (non-CHM cohort). Each cohort was matched 1:1 using the propensity score. Chi-square testing and the Student's t-test were used to examine differences between two cohorts. Cox proportional hazard regression analysis assessed the risks for major bleeding events in each cohort, as well as bleeding risks associated with specific CHM formulas and herbs. Cumulative incidence curves for major bleeding events were calculated using Kaplan-Meier analysis. RESULTS: Compared with the non-CHM cohort, the CHM cohort had a lower risk of overall bleeding events (p < 0.001) including hemorrhagic stroke (p = 0.008), gastrointestinal (GI) bleeding (p < 0.001), urogenital bleeding (p ≤ 0.001) and nasal/ear/eye bleeding (p = 0.004). Single herbs, such as Glycyrrhiza uralensis et Rhizoma, Panax notoginseng, Panax ginseng, Platycodon grandiflorum, Eucommia ulmoides Oliver and formulas, such as Shu Jing Huo Xue Tang, Shao Yao Gan Cao Tang and Ji Sheng Shen Qi Wan were associated with a lower risk of major bleeding events. CONCLUSION: Using CHMs with anticoagulants appeared to decrease the risk of major bleeding, especially CHMs products containing Glycyrrhiza uralensis et Rhizoma, Panax notoginseng, Panax ginseng, Platycodon grandiflorum and Eucommia ulmoides Oliver. Further investigations are needed to determine whether CHM can maintain the therapeutic efficacy of anticoagulants while simultaneously reducing potential side effects.

Aqueous extract of Solanum nigrum attenuates Angiotensin-II induced cardiac hypertrophy and improves cardiac function by repressing protein kinase C-ζ to restore HSF2 deSUMOlyation and Mel-18-IGF-IIR signaling suppression.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum nigrum, commonly known as Makoi or black shade has been traditionally used in Asian countries and other regions of world to treat liver disorders, diarrhoea, inflammatory conditions, chronic skin ailments (psoriasis and ringworm), fever, hydrophobia, painful periods, eye diseases, etc. It has been observed that S. nigrum contains substances, like steroidal saponins, total alkaloid, steroid alkaloid, and glycoprotein, which show anti-tumor activity. However; there is no scientific evidence of the efficacy of S. nigrum in the treatment of cardiac hypertrophy. AIM: To investigate the ability of S. nigrum to attenuate Angiotensin II - induced cardiac hypertrophy and improve cardiac function through the suppression of protein kinase PKC-ζ and Mel-18-IGF-IIR signaling leading to the restoration of HSF2 desumolyation. MATERIALS AND METHODS: Cardiomyoblast cells (H9c2) were challenged with 100 nM Angiotensin-II (AngII) for 24 h and were then treated with different concentration of S.nigrum or Calphostin C for 24 h. The hypertrophic effect in cardiomyoblast cells were determined by immunofluorescence staining and the modulations in hypertrophic protein marker along with Protein Kinase C-ζ, MEL18, HSF2, and Insulin like growth factor II (IGFIIR), markers were analyzed by western blotting. In vivo experiments were performed using 12 week old male Wistar Kyoto rats (WKY) and Spontaneously hypertensive rats (SHR) separated into five groups. [1]Control WKY, [2] WKY -100 mg/kg of S.nigrum treatment, [3] SHR, [4] SHR-100 mg/kg of S.nigrum treatment, [5] SHR-300 mg/kg of S.nigrum treatment. S. nigrum was administered intraperitoneally for 8 week time interval. RESULTS: Western blotting results indicate that S. nigrum significantly attenuates AngII induced cardiac hypertrophy. Furthermore, actin staining confirmed the ability of S. nigrum to ameliorate AngII induced cardiac hypertrophy. Moreover, S. nigrum administration suppressed the hypertrophic signaling mediators like Protein Kinase C-ζ, Mel-18, and IGFIIR in a dose-dependent manner and HSF2 activation (restore deSUMOlyation) that leads to downregulation of IGF-IIR expression. Additionally in vivo experiments demonstrate the reduced heart sizes of S. nigrum treated SHRs rats when compared to control WKY rats. CONCLUSION: Collectively, the data reveals the cardioprotective effect of S. nigrum inhibiting PKC-ζ with alleviated IGF IIR level in the heart that profoundly remits cardiac hypertrophy for hypertension-induced heart failure.

A Chinese Herbal Decoction, Modified Yi Guan Jian, Induces Apoptosis in Hepatic Stellate Cells through an ROS-Mediated Mitochondrial/Caspase Pathway.

The Chinese herb modified Yi Guan Jian (mYGJ) is an effective regimen that is usually used in outpatients with chronic liver diseases such as fibrosis and cirrhosis. However, the mechanism for the action of mYGJ on liver fibrosis is not yet clear. In this study, we found that mYGJ induced hepatic stellate cells (HSCs) apoptosis concomitant with the downregulation of Bcl-2 expression and slight elevation of Bax level. Moreover, the reactive oxygen species (ROS) were generated in the early stages of mYGJ-induced HSCs apoptosis to facilitate calcium and cytochrome c release from the mitochondria to cytosol. Subsequently, caspase 9 and caspase 3 were activated. Furthermore, the activation of ER stress-associated caspase 12 in HSCs was also evaluated. Together, we report the first evidence-based study to demonstrate that mYGJ decoction induces HSCs apoptosis through ROS accumulation and the intrinsic apoptosis pathway. These findings provide rationale for further clinical investigation of traditional Chinese medicine recipes against liver fibrosis.

Adipose derived mesenchymal stem cells along with Alpinia oxyphylla extract alleviate mitochondria-mediated cardiac apoptosis in aging models and cardiac function in aging rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The Fructus (Alpinia oxyphylla MIQ) known as Yi Zhi Ren in Chinese medicine has been used as a food and herbal medicinal substance in China for centuries; in the year 2015 Chinese Pharmacopoeia Commission reported water extracts of Alpinia oxyphyllae Fructus (AoF) as a popular medication for aging-related diseases in the form of tonic, aphrodisiac, and health-care food in south China. AIM OF THE STUDY: Adipose mesenchymal stem cells are physiologically and therapeutically associated with healthy vascular function and cardiac health. However aging conditions hinder stem cell function and increases the vulnerability to cardiovascular diseases. In this study, the effect of the anti-aging herbal medicine AoF to enhance the cardiac restorative function of adipose-derived mesenchymal stem cells (ADMSCs) in aging condition was investigated. MATERIALS AND METHODS: Low dose (0.1 µM) Doxorubicin and D-galactose (150 mg/kg/day for 8 weeks) were used to respectively induce aging in vitro and in vivo. For In vivo studies, 20 week old WKY rats were divided into Control, Aging induced (AI), AI + AoF, AI + ADMSC, AI + AoF Oral + ADMSC, and AI + AoF treated ADMSC groups. AoF (100 mg/kg/day) was administered orally and ADMSCs (1 × 106 cells) were injected (IV). RESULTS: AoF preconditioned ADMSC showed reduction in low dose Dox induced mitochondrial apoptosis and improved DNA replication in H9c2 cardiomyoblasts. In vivo experiments confirmed that both a combined treatment with AoF-ADMSCs and with AoF preconditioned ADMSCs reduced aging associated cardiac damages which was correlated with reduction in apoptosis and expression of senescence markers (P21 and ß-gal). Survival and longevity markers were upregulated up on combined administration of AoF and ADMSCs. The cardiac performance of the aging-induced rats was improved significantly in the treatment groups. AoF along with ADMSCs might activate paracrine factors to restore the performance of an aging heart. CONCLUSION: Hence, we propose that ADMSCs combined with AoF have promising therapeutic properties in the treatment of healthy aging heart.

Irritable bowel syndrome increases the risk of chronic obstructive pulmonary disease: A retrospective cohort study.

Both inflammation and infection are associated with the development of irritable bowel syndrome (IBS) and chronic obstructive pulmonary disease (COPD). The purpose of this study is to further elucidate the association between IBS and COPD through a retrospective cohort study. We enrolled IBS patients diagnosed between 2000 and 2011 with follow-up for at least one year. The non-IBS patients as comparison group were selected with 1:3 matching by propensity score. Statistical analysis was utilized to assess the differences in characteristic distribution, and to compare the cumulative incidence of COPD between the IBS and non-IBS cohorts. We selected 14,021 IBS patients and 42,068 non-IBS patients for comparison. The IBS patients exhibited a significant risk to develop COPD compared with non-IBS patients. Additionally, the cumulative incidence rate of COPD in the IBS cohort increased significantly during the follow-up period of more than ten years, compared to the non-IBS cohort, based on the Kaplan-Meier analysis. The risk of COPD was also significantly decreased in those patients with more than eighteen IBS-related clinical visits. This retrospective cohort study demonstrates the significantly increased risk of COPD in patients with IBS. Therefore, early inspection and prevention of COPD is essential for patients with IBS.

Principles and treatment strategies for the use of Chinese herbal medicine in patients at different stages of coronavirus infection.

Coronavirus disease 2019 (COVID-19) is a novel, human-infecting ß-coronavirus enveloped, positive-sense single-stranded RNA viruses, similar to the severe acute respiratory syndrome (SARS) infection that emerged in November 2002. In traditional Chinese medicine (TCM), the epidemic disease concepts of "febrile epidemics" (wenyi) or "warm diseases" (wenbing) are based on geographic and cultural aspects, and Chinese herbal medicine (CHM) played an important role in the treatment of epidemic diseases. CHM was widely used to treat patients suffered with SARS almost two decades ago during outbreak of SARS, with proven safety and potential benefits. TCM has also been widely used to treat cancer patients for a long history and much of them associate with immunomodulatory activity and are used to treat coronavirus-related diseases. We propose the use of CHM treatment principles for clinical practice, based on four main stages of COVID-19 infection: early, intermediate, severe, and convalescence. We suggest corresponding decoctions that exhibit antiviral activity and anti-inflammatory effects in the early stage of infection; preventing the disease from progressing from an intermediate to severe stage of infection; restoring normal lung function and improving consciousness in the severe stage; and ameliorating pulmonary and vascular injury in the convalescent stage. We summarize the pharmaceutical mechanisms of CHM for treating coronavirus via antiviral, anti-inflammatory and immunomodulatory effects.

Conventional Western Treatment Combined With Chinese Herbal Medicine Alleviates the Progressive Risk of Lung Cancer in Patients With Chronic Obstructive Pulmonary Disease: A Nationwide Retrospective Cohort Study.

Background and purpose: Lung cancer has high global incidence and mortality rates. Chronic obstructive pulmonary disease (COPD) is strongly associated with lung cancer and is an independent risk factor for lung cancer with or without smoking. Chinese herbal medicines (CHMs) are used to treat COPD. This study sought to determine whether CHM treatment effectively decreases the incidence of lung cancer in COPD patients receiving conventional Western medical treatment. Methods: Records obtained from the National Health Insurance Research Database (NHIRD) were used to identify 81,780 adults aged ≥18 years newly diagnosed with COPD in Taiwan between 2000 and 2010. Among them, 11,180 received CHMs after COPD diagnosis and 23,319 did not (non-CHM). After excluding patients with missing basic demographic information, each group consisted of 2,682 patients. Statistical methods analyzed the baseline characteristics for both groups and we performed a Cox proportional hazard regression analysis to examine the incidence of lung cancer. The cumulative incidence of lung cancer in COPD patients with or without CHM treatment was calculated by the Kaplan-Meier method. The association between herbs and formulas was examined by NodeXL to perform a network analysis of CHM. Results: COPD patients using CHM had a lower risk for lung cancer (adjusted hazards ratio [aHR] = 0.36, 95% confidence interval [CI] = 0.24-0.53, p < 0.001). Older age was associated with a higher risk of lung cancer: patients aged 40-59 years (aHR = 5.32, 95% CI = 2.19-12.94, p < 0.001) and those aged ≥60 years (aHR = 16.75, 95% CI = 7.54-37.23, p < 0.001) were at significantly greater risk compared with patients aged 18-39 years. CHM use was associated with a trend for a lower cumulative incidence of lung cancer compared with non-CHM use (p < 0.001). Among the 10 most commonly used single herbs and formulas used to decrease the risk of lung cancer in COPD patients, Fritillariae thunbergii was the most commonly used single herb and Xiao Qing Long Tang the most commonly used formula. Conclusion: The findings from this nationwide retrospective cohort study indicate that CHM as adjunctive therapy in COPD treatment regimens may reduce the risk of lung cancer in this vulnerable patient population.

Conventional Western Treatment Associated With Chinese Herbal Medicine Ameliorates the Incidence of Head and Neck Cancer Among Patients With Esophageal Cancer.

BACKGROUND: Because of advances in medical treatment, the survival of cancer patients is prolonged. In line with the prolonged survival time of cancer the incidence of second primary cancer has increased. There is currently no effective way to prevent the occurrence of secondary primary cancer (SPC). OBJECTIVES: The aim of this study is to evaluate whether Chinese Herbal Medicine (CHM) is correlated with reduced occurrence of second primary cancer (SPC) of head and neck (H&N) in patients with esophageal cancer (EC). METHOD: We identified 15,546 patients who were diagnosed with esophageal cancer between Jan 1, 2000, and Dec 31, 2010. The patients with H&N cancer before receiving CHM were excluded. After the selection and matching process, both CHM and non-CHM cohorts each contained 850 individuals. We compared the cumulative incidence of SPC of H&N with or without CHM treatment in patients with EC by the Kaplan-Meier method. NodeXL is used to run a network analysis of CHM to examine the association between herbs and formulas. RESULTS: Compared with non-CHM users, CHM-users showed a reduced incidence rate of SPC of H&N among the patients with EC. Reduced cumulative incidence of SPC of H&N among patients with EC was noted in the CHM cohort compared to the non-CHM cohort. The most commonly used single herbs and formulas were associated with reducing SPC occurrence. CONCLUSION: We propose that CHM as an adjuvant therapy may prevent the occurrence of SPC of H&N in patients with EC.