[Natural 5α-reductase inhibitors in treatment of benign prostatic hyperplasia].

Benign prostatic hyperplasia(BPH) is a common disease of the male urinary system, and its incidence rate in China is increasing. However, the mechanism underlying the pathogenesis of BPH remains unclear. Some studies demonstrated that the incidence of BPH was related to the change in the levels of steroid hormones. Too high content of dihydrotestosterone(DHT) in the body may cause BPH and other related diseases. Testosterone(T) is converted to DHT by 5α-reductase(SRD5A). By inhibiting the activity of this enzyme, the production of DHT can be reduced, and then the incidence of BPH can be lowered. Therefore, it has drawn great attention to screen and discover safer and more effective 5α-reductase inhibitors from natural medicines to treat prostatic hyperplasia without affecting the physiological function of men. This review summarizes the characteristics and tissue distribution of 5α-reductase, the discovery of 5α-reductase inhibitors in traditional Chinese medicine and natural medicines, 5α-reductase inhibitors commonly used in clinical practice and their side effects, as well as the animal models of prostatic hyperplasia and common detection indicators, aiming to provide a reference for more in-depth understanding and research about BPH and development of drugs.

Dietary supplementation of probiotics fermented Chinese herbal medicine Sanguisorba officinalis cultures enhanced immune response and disease resistance of crucian carp (Carassius auratus) against Aeromonas hydrophila.

Aeromonas hydrophila, a Gram-negative bacterium, is one of the major pathogens causing bacterial sepsis in aquatic animals due to drug resistance and pathogenicity, which could cause high mortality and serious economic losses to the aquaculture. Sanguisorba officinalis (called DiYu in Chinese, DY) is well known as herbal medicine, which could inhibit the growth of pathogenic bacteria, hemostasis and regulate the immune response. Moreover, the active ingredients in DY could remarkably reduce drug resistance. In this study, we investigated the effects of probiotic fermentation cultures on A. hydrophila through in vitro and in vivo experiments. Three lactic acid bacteria, including Lactobacillus rhamnosus (LGG), Lactobacillus casei (LC) and Lactobacillus plantarum (LP), were selected to ferment the Chinese herbal medicine DY. The assays of antagonism showed that all three fermented cultures could influence the ability of A. hydrophila growth, among which L. rhamnosus fermented DY cultures appeared to be the strongest inhibitory effect. In addition, the biofilm determination revealed that L. rhamnosus fermented DY cultures could significantly inhibit the biofilm formation of A. hydrophila compared to the other groups. Furthermore, protease, lecithinase and urease activities were found in the three fermentation cultures. Three probiotics fermented DY cultures were orally administration with crucian carp to evaluate the growth performance, immunological parameters and pathogen resistance. The results showed that the three fermentation cultures could promote the growth performance of crucian carp, and the immunoglobulins, antioxidant-related enzymes and immune-related genes were significantly enhanced. Besides, the results showed that crucian carp received L. rhamnosus (60.87%), L. casei (56.09%) and L. plantarum (41.46%) fermented DY cultures had higher survival rates compared with the control group after infection with A. hydrophila. Meanwhile, the pathological tissue results revealed that the probiotic fermented cultures could largely improve the tissues damage caused by the pathogenic bacteria. In conclusion, this study proved that the fermentation cultures of three probiotics could effectively inhibit the growth of A. hydrophila, regulate the level of immune response and improve the survival rate against A. hydrophila in crucian carp. The present data suggest that probiotic fermented Sanguisorba officinalis act as a potential gut-targeted therapy regimens to protecting fish from pathogenic bacteria infection.

Thermographic follow-up of postherpetic neuralgia (PHN) subsequent to Ramsay Hunt syndrome with multicranial nerve (V, VII, VIII and IX) involvement: a case report.

BACKGROUND: Ramsay Hunt syndrome (RHS) is caused by a reactivation of varicella-zoster virus (VZV) infection, and it is characterized by the symptoms of facial paralysis, otalgia, auricular rash, and/or an oral lesion. Elderly patients or immunocompromised patients, deep pain at the initial visit and no prompt treatment are significant predictors of postherpetic neuralgia (PHN). When PHN occurs, especially involved cranial polyneuropathy, multiple modalities should be administered for patients with the intractable PHN. The use of thermography in the follow-up of PHN secondary to RHS with multicranial nerve involvement has not yet been described yet in the literature. CASE PRESENTATION: The patient was a 78-year-old man with the chief complaint of a 3-month history of PHN secondary to RHS with polycranial nerve (V, VII, VIII, and IX) involvement. Multimodality therapy with oral gabapentin, pulsed radiofrequency (PRF) application to the Gasserian ganglion for pain in the trigeminal nerve region, linear-polarized near-infrared light irradiation for pain in the facial nerve region, and 2% lidocaine spray for pain in the glossopharyngeal nerve region was used to the treat patient, and follow-up evaluations included thermography. This comprehensive treatment obviously improved the quality of life, resulting in considerable pain relief, as indicated by a decrease in the numerical rating scale (NRS) score from 9 to 3 and a decrease in thermal imaging temperature from higher to average temperature on the ipsilateral side compared with the contralateral side. Lidocaine spray on the tonsillar branches of the glossopharyngeal nerve resulted in an improvement in odynophagia, and the NRS score decreased from 9 to 0 for glossopharyngeal neuralgia after three applications. CONCLUSION: Although the use of thermography in the follow-up of RHS with multiple cranial nerve (V, VII, VIII, and IX) involvement is very rare, in this patient, thermal imaging showed the efficacy of combination therapy (oral gabapentin, 2% lidocaine sprayed, PRF application and linear-polarized near-infrared light irradiation) and that is a good option for treatment.

Synthesis and In Vitro anti-HCV and Antitumor Evaluation of Schisandronic Acid Derivatives.

BACKGROUND: Schisandronic acid (SA), a triterpenoid from fruits of Schisandra sphenanthera, inhibited pan-genotypic HCV entry into human hepatocytes by interfering with virion-cell membrane fusion. It was a promising lead compound for the development of novel HCV entry inhibition agents. OBJECTIVE: The aim of the present study is to search for compounds with more potent anti-HCV and antitumor activities and explore SARs. A series of novel derivatives of SA were designed and synthesized and evaluated for in vitro, their anti-HCV and antitumor activities. METHODS: SA derivatives were synthesized by reduction, condensation, esterification or amidation. The anti-HCV activity of title compounds was tested by inhibition on HCVcc infection of Huh7 cells, and a preliminary MOA study was conducted by determining inhibition on HCVpp entry into Huh7 cells. The antitumor activity in vitro was determined by MTT methods. RESULTS: In total, 24 novel derivatives were synthesized. Most of the compounds inhibited HCVcc infection. Compounds 5h and 6 showed the most potent anti-HCVcc activities and inhibition of HCVpp entry into Huh7 cells without obvious cytotoxicity. Most of the title compounds showed potent in vitro antitumor activities against Bel7404 and SMMC7721 tumor cell lines. Compounds 5j and 6 exhibited more potent antitumor activity than positive control SA and DOX. CONCLUSION: Structural modification of SA could lead to the discovery of potent anti-HCV or antitumor agents. Compounds 5h, 5j and 6 were promising lead compounds for development of novel HCV entry inhibition or antitumor agents.

Synthesis and Anti-HCV Activities of 18ß-Glycyrrhetinic Acid Derivatives and Their In-Silico ADMET Analysis.

BACKGROUND: Licorice is widely used as a hepatoprotective herb for thousands of years in Traditional Chinese Medicine, and its main chemical constituent glycyrrhizin (GL) is used as a treatment for chronic hepatitis in Japan for over 20 years. 18ß-Glycyrrhetinic acid (GA) is the main active metabolite of GL. OBJECTIVE: Series of GA derivatives were designed and synthesized, and their anti-HCV activities were screened to investigate the structure-activity relationship (SAR). Besides, their in-silico ADMET properties were analyzed to search for a promising lead compound for further identification of anti-HCV terpenoid candidates. METHODS: GA derivatives were synthesized via reactions of oxidation, oxime, rearrangement, esterification and acylation. In vitro anti-HCV activity of derivatives was tested on the HCV cell culture (HCVcc) system. In-silico ADMET properties analysis was performed via "pkCSM" and "SwissADME" platforms. RESULTS: Eighteen GA derivatives were synthesized, and their structures were confirmed by MS and NMR spectrums. All compounds exhibited superior HCV inhibitory activity to that of GA. Compound 2 possessed the most potent anti-HCV activity with an IC50 value of 0.79 µM, which is nearly 58 times potent than SA (a previously reported potent anti-HCV terpenoids) and >200 times than GA. SAR revealed that the introduction of 3-oxo, short-chain (C1-C3) aliphatic alcohols or cyclic aliphatic amines is conducive to improving anti-HCV activity. In-silico ADMET prediction demonstrated most of the potent compounds possessed favorable ADMET properties. CONCLUSION: Structural modification of GA at 3-position and 30-position is an effective approach to searching for potent anti-HCV agents. Compound 2, with the most potent anti-HCV activity and favorable in-silico ADMET properties, is a promising lead compound for further identification of anti-HCV terpenoid candidates.

Periconceptional Folic Acid Supplementation and the Risk of Spontaneous Abortion among Women Who Prepared to Conceive: Impact of Supplementation Initiation Timing.

It is unclear whether periconceptional folic acid (FA) supplementation decreases the risk of spontaneous abortion (SA). The impact of supplementation initiation timing has not been ascertained. This cohort study aimed to investigate the association between maternal periconceptional FA supplementation and risk of SA, with due consideration of the supplementation initiation timing. Through the National Free Pre-conception Health Examination Project (NFPHEP), we identified 65,643 pregnancies on FA supplementation in Chongqing, China between 2010 and 2015. After adjusting for covariates, maternal periconceptional FA supplementation was associated with a lower risk of SA (adjusted risk ratio [aRR]: 0.52; 95% confidence interval [CI]: 0.48-0.56). Pregnant women with FA supplementation initiated at least 3 months before conception had a 10% lower risk of SA (aRR: 0.46; 95% CI: 0.42-0.50) than those with FA supplementation initiated 1-2 months before conception (aRR: 0.56; 95% CI: 0.50-0.62) or after conception (aRR: 0.56; 95% CI: 0.51-0.61). These associations might not thoroughly account for FA supplementation, and to some extent our findings confirm the role of the utilization of healthcare in preventing SAs. Women who initiated healthcare, including taking FA earlier during the periconceptional period, could have a lower risk of SA.

Protecting HaCaT cells from ionizing radiation using persimmon tannin-Aloe gel composite.

Context: Persimmon tannin (extract of Diospyros kaki L.f [Ebenaceae]) and Aloe gel (extract of Aloe vera (L.) Burm.f. [Asphodelaceae]) are known as anti-radiation agents. However, radiation resistance of the persimmon tannin-Aloe gel composite remains inconclusive.Objective: To investigate the capacity of the persimmon tannin-Aloe gel composite to protect against ionising radiation at the cellular level.Materials and methods: HaCaT (human epidermal keratinocytes) cells were pre-treated with PT-A-1 (the mass ratio of persimmon tannin and Aloe gel was 2:1) or the single component (persimmon tannin or Aloe gel) at various concentrations (0, 50, 100, 200, 400, 800 µg/mL. Control group: medium with no HaCaT cells), and then radiated with X-rays (radiation dose: 4, 8, 12, 16, and 20 Gy). Cell viability, cell apoptosis, and radiation-induced intracellular reactive oxygen species (ROS) generation were analysed by CCK-8, Hoechst 33258 staining/flow cytometry, and 2',7'-dichlorfluorescein diacetate (DCFH-DA) assay, respectively, for 12 or 24 h incubation after radiation.Results: The optimal radiation dose and post-radiation incubation period were determined to be 8 Gy and 12 h. CCK-8 activity detection showed that the cell activity was 77.85% (p < 0.05, IC50 = 55.67 µg/mL). The apoptotic rate was the lowest (4.32%) at 200 µg/mL of PT-A-1 towards HaCaT cells. ROS production was the most effectively suppressed by 200 µg/mL PT-A-1 towards HaCaT cells.Discussion and conclusions: The persimmon tannin-Aloe gel composite has good radioprotective effect, and which will facilitate its clinic application as a potential natural anti-radiation agent in future.

A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes.

Despite recent progress in the development of hepatitis C virus (HCV) inhibitors, cost-effective antiviral drugs, especially among the patients receiving liver transplantations, are still awaited. Schisandra is a traditional medicinal herb used to treat a range of liver disorders including hepatitis for thousands of years in China. To isolate the bioactive compounds of schisandra for the treatment of HCV infection, we screened a schisandra-extracts library and identified a tetracyclic triterpenoid, schizandronic acid (SZA), as a novel HCV entry inhibitor. Our findings suggested that SZA potently inhibited pan-HCV genotype entry into hepatoma cells and primary human hepatocytes without interfering virus binding on cell surface or internalization. However, virion-cell fusion process was impaired in the presence of SZA, along with the increased host membrane fluidity. We also found that SZA inhibited the spread of HCV to the neighboring cells, and combinations of SZA with interferon or telaprevir resulted in additive synergistic effect against HCV. Additionally, SZA diminished the establishment of HCV infection in vivo. The SZA target is different from conventional direct-acting antiviral agents, therefore, SZA is a potential therapeutic compound for the development of effective HCV entry inhibitors, especially for patients who need to prevent HCV reinfection during the course of liver transplantations.