Medicinal plants and natural products for treating overactive bladder.

BACKGROUND: Overactive bladder (OAB) presents a high prevalence of 16-18% worldwide. The pathophysiology of OAB is still poorly understood while effective therapy or countermeasure are very limited. On the other hand, medicinal plants and herbal remedies have been utilized for treating lower urinary tract symptoms (LUTS) in both Eastern and Western cultures since ancient times. In recent years, accumulating progress has also been made in OAB treatment research by using medicinal plants. METHODS: Relevant literature on the studies of medicinal plants and herbs used to treat OAB was reviewed. The medicinal plants were summarized and categorized into two groups, single-herb medications and herbal formulations. RESULTS: The present review has summarized current understanding of OAB's pathophysiology, its available treatments and new drug targets. Medicinal plants and natural products which have been used or have shown potential for OAB treatment were updated and comprehensively categorized. Studies on a wide variety of medicinal plants showed promising results, although only a few phytochemicals have been isolated and identified. Until now, none of these herbal compounds have been further developed into clinical therapeutics for OAB. CONCLUSIONS: This review provides the basis for discovering and designing new phytopharmaceutical candidates with effective and well-tolerated properties to treat OAB. Increasing evidences indicate new strategies with alternative herbal treatment for OAB have high efficacy and safety, showing great promise for their clinical use. Future studies in a rigorously designed controlled manner will be beneficial to further support the eligibility of herbal treatment as OAB therapeutics.

Quantitative measurements of zebrafish heartrate and heart rate variability: A survey between 1990-2020.

Zebrafish is an essential model organism for studying cardiovascular diseases, given its advantages of fast proliferation and high gene homology with humans. Zebrafish embryos/larvae are valuable experimental models used in toxicology studies to analyze drug toxicity, including hepatoxicity, nephrotoxicity and cardiotoxicity, as well as for drug discovery and drug safety screening in the preclinical stage. Heart rate (HR) serves as a functional endpoint in studies of cardiotoxicity, while heart rate variability (HRV) serves as an indicator of cardiac arrhythmia. Cardiotoxicity is a major cause of early and late termination of drug trials, so a more comprehensive understanding of zebrafish HR and HRV is important. This review summarized HR and HRV in a specific range of applications and fields, focusing on zebrafish heartbeat detection procedures, signal analysis technology and well-established commercial software, such as LabVIEW, Rvlpulse, and ZebraLab. We also compared HR detection algorithms and electrocardiography (ECG)-based methods of heart signal extraction. The relationship between HR and HRV was also systematically analyzed; HR was shown to have an inverse correlation with HRV. Applications to drug testing are also highlighted in this review. Furthermore, HR and HRV were shown to be regulated by the automatic nervous system; their connections with ECG measurements are also summarized herein.

Determination of Oxyphylla A Enantiomers in the Fruits of Alpinia oxyphylla by a Chiral High-Performance Liquid Chromatography-Multiple Reaction Monitoring-Mass Spectrometry Method and Comparison of Their In Vivo Biological Activities.

(R)-Oxyphylla A, a natural product isolated from Alpinia oxyphylla Miquel as a food and medicinal plant, has been reported previously as a novel chiral compound that possesses a potential therapeutic value for Parkinson's disease (PD). A chiral high-performance liquid chromatography-multiple reaction monitoring-mass spectrometry method was developed to separate oxyphylla A enantiomers and to identify the presence of natural (S)-oxyphylla A for the first time. Twelve samples of dried A. oxyphylla fruits were analyzed in which a large variation in the abundance of enantiomers was observed. Moreover, (S)-oxyphylla A was less abundant in all tested samples, whereas fruits harvested from Hainan and Guangdong tended to have relatively higher total concentrations of enantiomers. Additionally, enantiomers exhibited comparable neuroprotective effects in the zebrafish model of PD without observed toxicity phenotype. The optimized enantioseparation method will be crucial for the quality control of A. oxyphylla and research on bioactivities facilitates the development of oxyphylla A as a potential therapeutic for neurodegenerative diseases.

Synergistic effect of fenretinide and curcumin for treatment of non-small cell lung cancer.

Curcumin and fenretinide are 2 well-known and promising chemotherapeutic compounds via various molecular mechanisms. However, the anticancer capacity of either curcumin or fenretinide is limited. This prompted us to examine the combined anticancer effects of curcumin and fenretinide. Our results demonstrate for the first time that there is synergistic anticancer effect of combined treatment with these 2 agents, leading to enhanced cytotoxicity and enhanced expression level of pro-apoptotic protein cleaved PARP in non-small cell lung cancer (NSCLC) cells while showed little toxicity to rat cardiomyoblast normal cells. The combination treatment was also demonstrated to inhibit lung carcinoma growth in vivo. Furthermore, we show that fenretinide or the ER stress inhibitor 4-PBA decreased curcumin-induced Glucose-regulated protein 78 (GRP78) upregulation, and produced a similar enhanced cytotoxic effect. In addition, GRP78 knockdown by siRNA also enhanced the cytotoxic effect of curcumin in A549 and H1299 cells. Our findings suggest that the 2 small molecules, when used in combination, can potentially be effective therapeutic agents for treating NSCLC, at least in part, by regulating endoplasmic reticulum (ER) chaperone protein GRP78.

FGF2 Prevents Sunitinib-Induced Cardiotoxicity in Zebrafish and Cardiomyoblast H9c2 Cells.

Sunitinib is used extensively in the treatment of metastatic renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumors. However, the undesirable cardiotoxic effects of sunitinib, such as congestive heart failure and hypertension, limit its use in the clinical setting. As multiple receptor tyrosine kinases are inhibited by sunitinib, it raises a question as to which target mediates sunitinib-induced cardiotoxicity. Here, we reported that the injection of fibroblast growth factor 2 (FGF2) mRNA into one- to two-cell stage embryos protected against sunitinib-induced cardiotoxicity in zebrafish. In addition, FGF2 significantly prevented sunitinib-induced cardiotoxicity in cardiomyoblast H9c2 cells, possibly via activating the PLC-γ/c-Raf/CREB pathway. Importantly, FGF2 did not compromise the antitumor activity of sunitinib in Caki-1 and OS-RC-2 renal cell carcinoma cells. Molecular docking simulations further revealed an interaction between the tyrosine kinase domain of FGF receptor 1 (FGFR1) and sunitinib. Taken together, our results clearly demonstrated that FGF2 inhibition plays an important role in sunitinib-induced cardiotoxicity both in vitro and in vivo. This study also provided a basis for further research on sunitinib-induced cardiotoxicity and may allow rational design of new sunitinib derivatives with fewer or weak cardiotoxic effects.

A Novel Danshensu Derivative Prevents Cardiac Dysfunction and Improves the Chemotherapeutic Efficacy of Doxorubicin in Breast Cancer Cells.

Doxorubicin (Dox) is an anthracycline antibiotic widely used in clinics as an anticancer agent. However, the use of Dox is limited by its cardiotoxicity. We have previously shown that a Danshensu (DSS) derivative, ADTM, displayed strong cardioprotective effects. With improved chemical stability and activity, a novel DSS derivative, D006, based on the structure of ADTM, was synthesized. In the present study, the protective effects of D006, indexed by attenuation of the cardiotoxicity induced by Dox as well as chemosensitizing effects that increase the antitumor activity of Dox, were investigated. Our results showed that D006 was more potent than either parental compound, or their use in combination, in ameliorating Dox-induced toxicity in H9c2 cells. In our zebrafish model, D006, but not DSS, alone significantly preserved the ventricular function of zebrafish after Dox treatment. Moreover, D006 upregulated mitochondrial biogenesis and increased mtDNA copy number after Dox treatment of H9c2 cells. D006 promoted the expression of HO-1 protein in a time-dependent manner while the HO-1 inhibitor, Znpp, reversed the protective effects of D006. In human breast tumor MCF-7 cells, D006 enhanced Dox-induced cytotoxicity by increasing apoptosis. In conclusion, our results indicate that a new DSS derivative exhibits promising protective effects against Dox-induced cardiotoxicity both in vivo and in vitro, an effect at least partially mediated by induction of HO-1 expression and the activation of mitochondrial biogenesis. Meanwhile, D006 also potentiated the anti-cancer effects of Dox in breast tumor cells.

Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor.

Cucurbit[7]uril (CB[7]) was found in vitro to sequester the neurotoxins MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP(+) (N-methyl-4-phenylpyridine). The CB[7]/neurotoxin host-guest complexes were studied in detail with (1)H NMR, electrospray ionization mass spectrometry, UV-visible spectroscopic titration, and molecular modeling by density functional theory. The results supported the macrocyclic encapsulation of MPTP and MPP(+), respectively, by CB[7] in aqueous solutions with relatively strong affinities and 1:1 host-guest binding stoichiometries in both cases. More importantly, the progression of MPTP/MPP(+) induced neurodegeneration (often referred to as a Parkinson's disease model) was observed to be strongly inhibited in vivo by the synthetic CB[7] receptor, as shown in zebrafish models. These results show that a supramolecular approach could lead to a new preventive and/or therapeutic strategy for counteracting the deleterious effects of some neurotoxins leading to neurodegeneration.

Treatment of Benign Prostatic Hyperplasia by Ultrasound-Guided Botulinum Toxin Type A Injection.

The objective of the study was to determine the efficacy of ultrasound-guided botulinum toxin type A (BTX-A) injection in the treatment of benign prostatic hyperplasia (BPH). In the 32 patients clinically diagnosed with BPH, 200 IU BTX-A was injected into five points at the lateral and middle lobes of the prostate under the guidance of ultrasound using a balloon dilatational device. The international prostate symptom score, quality of life score, maximum flow rate, post-void residual urine volume, prostate-specific antigen, and prostate volume were determined before treatment and at 1, 3, 6, and 12 months after treatment. All clinical symptoms and indicators were remarkably improved 1 month after the treatment and reached the optimal levels at 6 months post-treatment. This improvement of clinical parameters was maintained for a period of at least 1 year. Ultrasound-guided BTX-A injection was found to be safe and effective in the management of BPH.

[Study on treatment of climacteric depression with bushen tiaogan qingxin recipe].

OBJECTIVE: To observe the effects of bushen tiaogan qingxin recipe (BTQR) on Hamilton rating scale for depression (HAMD), monoamine meurotransmitter and endocrinal function in patients with climacteric depression, and to explore its mechanism. METHODS: Patients were randomly divided into two groups, the 25 patients in the treated group treated with BTQR and 15 patients in the control group treated with hormone replacement therapy (HRT). The HAMD scoring, levels of 5-HT, NE in plasma, serum estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH) were determined before and after treatment, and the thickness of endometrium was measured by B-Doppler ultrasonographic technique. RESULTS: The total effective rate, evaluated by the HAMD score reducing rate, in the treated group was 87.2%, and in the control group was 67.3%, showing significant difference (P<0.05). After treatment, 5-HT decreased (P<0.01), NE increased (P<0.05) and 5-HT/NE ratio lowered (P<0.01) in the treated group; E2 increased in both groups; FSH, LH and FSH/LH ratio decreased in the treated group (P<0.05 or P<0.01), FSH/LH ratio decreased in the control group (P<0.05). The thickness of endometrium increased in the control group after treatment (P<0.05). CONCLUSION: The mechanism of BTQR in treating climacteric depression might be related with its actions in: (1) To regulate the synthesis and release of monoamine neurotransmitter; (2) To adjust reproductive endocrine function; (3) To coordinate the neuroendocrinal function.