Research Progress on Natural Products' Therapeutic Effects on Atrial Fibrillation by Regulating Ion Channels.

Antiarrhythmic drugs (AADs) have a therapeutic effect on atrial fibrillation (AF) by regulating the function of ion channels. However, several adverse effects and high recurrence rates after drug withdrawal seriously affect patients' medication compliance and clinical prognosis. Thus, safer and more effective drugs are urgently needed. Active components extracted from natural products are potential choices for AF therapy. Natural products like Panax notoginseng (Burk.) F.H. Chen, Sophora flavescens Ait., Stephania tetrandra S. Moore., Pueraria lobata (Willd.) Ohwi var. thomsonii (Benth.) Vaniot der Maesen., and Coptis chinensis Franch. have a long history in the treatment of arrhythmia, myocardial infarction, stroke, and heart failure in China. Based on the classification of chemical structures, this article discussed the natural product components' therapeutic effects on atrial fibrillation by regulating ion channels, connexins, and expression of related genes, in order to provide a reference for development of therapeutic drugs for atrial fibrillation.

Research Progress on the Mechanism of Natural Product Ingredients in the Treatment of Uveitis.

BACKGROUND: As the spectrum of ophthalmic diseases keeps changing, uveitis has gradually become one of the major blinding eye diseases in the world. In recent years, it has become a research hotspot to select effective components for uveitis treatment from natural drugs. METHODS: We searched PubMed and EMBASE databases for studies written in English as well as Chinese National Knowledge Infrastructure (CNKI), CQVIP, and Wan Fang database for studies written in Chinese (inception through 30 December 2020). RESULTS: Eight kinds of natural product ingredients were included in this article. They were found to not only regulate the expression of cytokines, proliferation, and differentiation of T help cells but also inhibit the damage of cytokines and inflammatory cells to uvea, blood aqueous barrier, and blood retinal barrier. CONCLUSION: Natural product ingredients have their unique advantages in the treatment of uveitis. They have good anti-inflammatory effects without causing serious adverse reactions, which enables them to be promising choices for preventive and therapeutic strategy of uveitis.

Borneol influences the pharmacokinetics of florfenicol through regulation of cytochrome P450 1A2 (CYP1A2), CYP2C11, CYP3A1, and multidrug resistance 1 (MDR1) mRNA expression levels in rats.

Borneol is a traditional Chinese medicine. In Chinese veterinary clinics, borneol and its related compounds are often used in combination with florfenicol to treat respiratory infections. This study investigated whether the pharmacokinetics of florfenicol in rats was affected by its concomitant use with borneol. Sprague-Dawley rats were intragastrically administered borneol (50 mg/kg body weight (BW)) or 0.5% carboxymethyl-cellulose sodium for 7 consecutive days, and then intragastrically administered florfenicol (25 mg/kg BW) on the eighth day. Pharmacokinetic studies showed that borneol significantly decreased the area under the concentration-time curve from zero to infinity (AUC(0-t)), time to reach peak concentration (Tmax), and the peak concentration (Cmax) values of florfenicol, whereas the values of mean residence time from zero to infinity (MRT(0-t)), elimination half-life (t1/2z), apparent volume of distribution fraction of the dose absorbed (Vz), and plasma clearance fraction of the dose absorbed (CLz) were increased significantly. Furthermore, the mRNA expression levels of multidrug resistance 1 (MDR1) and cytochrome P450 3A1 (CYP3A1) in the jejunum and of CYP1A2 and CYP2C11 in the liver were significantly upregulated by borneol. In conclusion, borneol decreased absorption, increased clearance, improved distribution, and increased the mean residence time of florfenicol in rats, possibly through regulating the mRNA expression levels of drug-metabolizing enzymes and efflux transporters.

Research Progress on Natural Product Ingredients' Therapeutic Effects on Parkinson's Disease by Regulating Autophagy.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and older adults. Abnormal proteins such as α-synuclein are essential factors in PD's pathogenesis. Autophagy is the main participant in the clearance of abnormal proteins. The overactive or low function of autophagy leads to autophagy stress. Not only is it difficult to clear abnormal proteins but also it can cause damage to neurons. In this article, the effects of natural products ingredients, such as salidroside, paeoniflorin, curcumin, resveratrol, corynoxine, and baicalein, on regulating autophagy and protecting neurons were discussed in detail to provide a reference for the research and development of drugs for the treatment of PD.

Research Progress on Anti-Inflammatory Effects and Mechanisms of Alkaloids from Chinese Medical Herbs.

As the spectrum of diseases keeps changing and life pace keeps going faster, the probability and frequency of diseases caused by human inflammatory reactions also keep increasing. How to develop effective anti-inflammatory drugs has become the hotspot of researches. It has been found that alkaloids from Chinese medical herbs have anti-inflammatory, analgesic, antitumor, anticonvulsant, diuretic, and antiarrhythmic effects, among which the anti-inflammatory effect is very prominent and commonly used in the treatment of rheumatoid arthritis, ankylosing spondylitis, and other rheumatic immune diseases, but its mechanism of action has not been well explained. Based on this, this paper will classify alkaloids according to structural types and review the plant sources, applicable diseases, and anti-inflammatory mechanisms of 16 kinds of alkaloids commonly used in clinical treatment, such as berberine, tetrandrine, and stephanine, with the aim of providing a reference for drug researches and clinical applications.

Carboxymethyl chitosan-zinc(II) phthalocyanine conjugates: Synthesis, characterization and photodynamic antifungal therapy.

Photodynamic antifungal therapy is a promising treatment for increasing drug-resistant fungi. However, low physiological solubility and low fungi-affinity of most potential photosensitizers limits their therapeutic efficacy. To improve the water-solubility and photodynamic antifungal activity of zinc(II) phthalocyanine, two molecular-weight carboxymethyl chitosans (CMC1,50 kDa; CMC2,170 kDa) were herein respectively conjugated with 1-[4-(2-aminoethyl)phenoxy] zinc(II) phthalocyanine (ZnPcN) and further quaternized, and eight novel conjugates were obtained and characterized. Their photophysical and photochemical properties, cellular uptakes and in vitro photodynamic antifungal activities against Candida albicans have also been investigated. All the conjugates are less aggregated in water than ZnPcN. The low-molecular-weight CMC1-conjugated ZnPcN is more readily ingested and highly photoactive. Mainly due to its highest uptake by Candida cells, a conjugate of CMC1 and ZnPcN shows the highest photocytotoxicity with an IC90 value down to 0.72 µM. Further quaternization decreases the photocytotoxicity. Additionally, the conjugates show special affinity to the mitochondria of C. albicans.

Effects of anemoside B4 on pharmacokinetics of florfenicol and mRNA expression of CXR, MDR1, CYP3A37 and UGT1E in broilers.

Pulsatillae radix, a traditional Chinese medicine (TCM), is often used in combination with florfenicol for treatment of intestinal infection in Chinese veterinary clinics. Anemoside B4 (AB4) is the major effective saponin in Pulsatillae radix. This study aimed to investigate whether the pharmacokinetics of florfenicol in broilers was affected by the combination of AB4. In this study, broilers were given AB4 (50 mg/kg BW), or 0.9% sodium chloride solution by oral administration for 7 days. They were then fed florfenicol orally (30 mg/kg BW) on the eighth day. The results showed that the AUC(0-∞), MRT(0-∞), t1/2z and Cmax of florfenicol were significantly decreased, and the Vz/F and CLz/F were significantly increased by AB4; the mRNA expression levels of CXR, CYP3A37 and MDR1 (except CXR and CYP3A37 in the liver) were up-regulated by AB4. In conclusion, AB4 altered the pharmacokinetics of florfenicol, resulting in lower plasma concentrations of florfenicol, this was probably related to the mRNA expression of CXR, CYP3A37 and MDR1 in the jejunum and liver (except CXR and CYP3A37) increased by AB4. The implications of these findings on the effect of traditional Chinese medicine containing AB4 on the effectiveness of florfenicol in veterinary practice deserve study.

Research Progress of Male Reproductive Toxicity of Chinese Materia Medicas.

In recent years, as the infertility rate in China has been increasing year by year and semen quality decreasing, male reproductive toxicity of drugs attracts more and more attention. There are many factors that cause male reproductive toxicity, among which Chinese materia medica is an important aspect. This article will introduce the male reproductive toxicity of Chinese materia medicas grouped by different effectivenesses such as immunosuppressant, evacuant, diuretic, cardiotonic, anti-infective drug and analgesic.

Phase I trial of concurrent stereotactic body radiotherapy and nelfinavir for locally advanced borderline or unresectable pancreatic adenocarcinoma.

INTRODUCTION: The HIV protease inhibitor nelfinavir (NFV) displays notable radiosensitizing effects. There have been no studies evaluating combined stereotactic body radiotherapy (SBRT) and NFV for borderline/unresectable pancreatic cancer. The primary objective of this phase I trial (NCT01068327) was to determine the maximum tolerated SBRT/NFV dose, and secondarily evaluate outcomes. METHODS: Following initial imaging, pathologic confirmation, and staging laparoscopy, subjects initially received three 3-week cycles of gemcitabine/leucovorin/fluorouracil; patients without radiologic progression received 5-fraction SBRT/NFV. Dose escalation was as follows: (1) 25 Gy/625 mg BID ×3wks; (2) 25 Gy/1250 mg BID ×3wks; (3) 30 Gy/1250 mg BID ×3wks; (4) 35 Gy/1250 mg BID ×3wks; (5) 35 Gy/1250 mg BID ×5wks; and (6) 40 Gy/1250 mg BID ×5wks. Pancreaticoduodenectomy was performed thereafter if resectable; if not, gemcitabine/leucovorin/fluorouracil was administered. RESULTS: Forty-six patients enrolled (10/2008-5/2013); 39 received protocol-directed therapy. Sixteen (41%) experienced any grade ≥2 event during and 1 month after SBRT. Four grade 3 and both grade 4 events occurred in a single patient at the initial dose level. 40 Gy/1250 mg BID ×5wks was the maximum tolerated dose. Five patients had late gastrointestinal bleeding (n = 2 superior mesenteric artery pseudo-aneurysm, n = 1 disease progression, n = 1 lower GI tract, n = 1 unknown location). The median overall survival was 14.4 months. Six (15%) patients recurred locally; median local failure-free survival was not reached. The median distant failure-free survival was 11 months, and median all failure-free survival was 10 months. CONCLUSIONS: Concurrent SBRT (40 Gy)/NFV (1250 mg BID) for locally advanced pancreatic cancer is feasible and safe, although careful attention to treatment planning parameters is recommended to reduce the incidence of late gastrointestinal bleeding.

Acupuncture Compared with Intramuscular Injection of Neostigmine for Postpartum Urinary Retention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To compare the effectiveness and safety of acupuncture versus intramuscular injection of neostigmine. METHODS: Databases including CNKI, VIP, WanFang, SinoMed, PubMed, Cochrane Library, and clinicaltrials.gov database were retrieved for relevant literature, with the retrieval deadline being November 2017. Two reviewers independently screened, selected, and extracted data and validated the results. The methodological quality was evaluated with the "Risk of Bias" tool, and the meta-analysis was performed by using the RevMan 5.3.5 software. RESULTS: Totally 953 patients with postpartum urinary retention from 15 randomized controlled trials entered the meta-analysis. 12 articles compared the clinical cure rate of acupuncture alone versus intramuscular injection of neostigmine and found the cure rate in the acupuncture group was 2 times that in the neostigmine group (RR, 1.91; 95% CI: 1.66-2.19). 15 articles compared the clinical effectiveness rate of acupuncture alone with that of intramuscular injection of neostigmine and found the clinical effectiveness rate was 28% higher in the acupuncture group than in the neostigmine group (RR: 1.28; 95% CI: 1.16-1.42). No adverse event was reported in the acupuncture group. CONCLUSION: Acupuncture alone is more effective in treating postpartum urinary retention than intramuscular injection of neostigmine, with good safety profile. Therefore, it is a feasible and valuable technique in clinical settings.

Identification and quantitation of phenolic compounds from the seed and pomace of Perilla frutescens using HPLC/PDA and HPLC-ESI/QTOF/MS/MS.

INTRODUCTION: Perilla frutescens (L.) Britt., an essential traditional Asian crop and Chinese medicine, potentially exerts anti-oxidation effects through its phenolic compounds. These compounds have already been reported in perilla seed, however, little is reported in Perilla pomace, the primary waste during oil production of Perilla seed. OBJECTIVE: To investigate major phenolic compounds in perilla seeds and pomaces in order to check whether the pomace could be an alternative resource to the seed for nutritional and medical purposes. METHODS: Compounds in extracts of perilla seeds and pomaces were separated by high-performance liquid chromatography and detected by photodiode array, and by electrospray ionisation with quadrupole time-of-flight tandem mass spectrometry. Herb-markers selected by principal components analysis were then quantified in both seeds and pomaces. Moreover, a fingerprinting approach and multiple discriminant analysis were applied to screen the phenolic markers in 22 samples. RESULTS: Ten phenols were tentatively identified, among which four (rosmarinic acid, luteolin, apigenin and rosmarinic acid-3-O-glucoside) were selected as herb-markers. Perilla seeds and pomaces showed similar phenol profiles, however, the pomaces contained almost two times the amount of the four herb-markers than the seeds. CONCLUSION: The results indicated perilla pomace is a promising alternative source of phenolic compounds that could be recovered and potentially used as natural anti-oxidants.