[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.

New chlorophenolic glycoside from Curculigo orchioides and their activities on 5α-reductase.

Two new chlorophenolic glucosides curculigines P (1) and Q (2), together with seven known compounds (3-9), were isolated from the dried rhizomes of Curculigo orchioides. Their structures were determined by spectroscopic methods including 1 D, 2 D NMR and MS. All the isolated compounds were evaluated on 5α-reductase activity by a HaCaT-based bioassay. Compounds 1-9 showed varying degrees of inhibiting activity against 5α-reductase, while compound 1 indicated the most potent inhibitory effect.[Formula: see text].

Fully automated chip-based nanoelectrospray ionization-mass spectrometry as an effective tool for rapid and high-throughput screening of 5α-reductase inhibitors.

The 5α-reductase converts testosterone to dihydrotestosterone (DHT), and excess DHT could cause androgen-related diseases such as androgenetic alopecia and benign prostatic hyperplasia (BPH). To discover new 5α-reductase inhibitors, effective drug screening method with high throughput is thus essential. In this study, fully automated chip-based nanoelectrospray ionization-mass spectrometry (nano-ESI-MS) was innovatively utilized as a screening tool for 5α-reductase inhibitory assay in direct infusion mode, which simplified sample pretreatment and greatly improved experimental efficiency. The preliminary data indicated that curcumin, a natural anti-inflammatory compound, exhibited notably 5α-reductase inhibition activity. Moreover, the obtained results of the chip-based nano-ESI-MS were well consistent with those of HPLC-MS, which suggested that the chip-based nano-ESI-MS could be treated as a rapid and high-throughput drugs screening strategy in pharmaceutical development. Graphical abstract.

Characterization of carotenoids in Lycium barbarum fruit by using UPC2-PDA-Q-TOF-MSE couple with deep eutectic solvents extraction and evaluation of their 5α-reductase inhibitory activity.

Carotenoids from Lyciu m barbarum fruits have possessed pharmacological efficacy against eye diseases, cardiovascular disorders, cancer, and benign prostatic hyperplasia. However, the efficient extraction, rapid characterization and activities evaluation of Lycium carotenoids remains a challenge. To concentrate and characterize Lycium carotenoids, we have developed ultrasound-assisted extraction methods with different deep eutectic solvents (DESs) and analyzed carotenoids by ultra-performance convergence chromatography coupled with photo diode array detector and quadrupole time-of-flight mass spectrometry (UPC2-PDA-Q-TOF-MSE). DESs containing choline chloride and malonic acid presented better extraction efficiency and were more environmentally friendly than other extraction methods. Carotenoids were more quickly profiled (in 11 min) by UPC2 compared to by UPLC (in 35 min), with seventeen main peaks were characterized in the MS fragmentation patterns. The in vitro 5α-reductase inhibitory activity of DESs extracts, fractions and components were subsequently assessed, and the predominant component zeaxanthin dipalmitate (ZD) exhibited potent inhibitory activity. Our study provides a chemical and pharmacological basis for the further development of potential new drugs based on Lycium carotenoids.

Intestinal AMPK modulation of microbiota mediates crosstalk with brown fat to control thermogenesis.

The energy-dissipating capacity of brown adipose tissue through thermogenesis can be targeted to improve energy balance. Mammalian 5'-AMP-activated protein kinase, a key nutrient sensor for maintaining cellular energy status, is a known therapeutic target in Type II diabetes. Despite its well-established roles in regulating glucose metabolism in various tissues, the functions of AMPK in the intestine remain largely unexplored. Here we show that AMPKα1 deficiency in the intestine results in weight gain and impaired glucose tolerance under high fat diet feeding, while metformin administration fails to ameliorate these metabolic disorders in intestinal AMPKα1 knockout mice. Further, AMPKα1 in the intestine communicates with brown adipose tissue to promote thermogenesis. Mechanistically, we uncover a link between intestinal AMPKα1 activation and BAT thermogenic regulation through modulating anti-microbial peptide-controlled gut microbiota and the metabolites. Our findings identify AMPKα1-mediated mechanisms of intestine-BAT communication that may partially underlie the therapeutic effects of metformin.

Advances on hormone-like activity of Panax ginseng and ginsenosides.

Traditional Chinese medicine (TCM) has been paid much attentions due to the prevention and treatment of steroid hormone disorders. Ginseng, the root of Panax ginseng C. A. Meyer (Araliaceae), is one of the most valuable herbs in complementary and alternative medicines around the world. A series of dammarane triterpenoid saponins, also known as phytosteroids, were reported as the primary ingredients of Ginseng, and indicated broad spectral pharmacological actions, including anti-cancer, anti-inflammation and anti-fatigue. The skeletons of the dammarane triterpenoid aglycone are structurally similar to the steroid hormones. Both in vitro and in vivo studies showed that Ginseng and its active ingredients have beneficial hormone-like role in hormonal disorders. This review thus summarizes the structural similarities between hormones and dammarane ginsenosides and integrates the analogous effect of Ginseng and ginsenosides on prevention and treatment of hormonal disorders published in recent twenty years (1998-2018). The review may provide convenience for anticipate structure-function relationship between saponins structure and hormone-like effect.

[Tinnitus with normal hearing and evoked otoacoustic emissions].

OBJECTIVE: To investigate the objective methods for tinnitus exploration by analysing the cochlear activity in tinnitus patients with normal hearing. METHOD: The 50 cases (50 ears) of unilateral tinnitus with normal hearing (the plastic group 1), 24 cases (46 ears) of bilateral tinnitus with normal hearing(the plastic group 2) and the 34 persons (68 ears) of normal hearing without tinnitus (control group) were measured by evoked otoacoustic emissions (TEOAE and DPOAE). All the tinnitus patients were also tested by the subjective tinnitus frequency and analysed with appropriate characteristic in TEOAE and DPOAE audiogram. RESULT: (1) The passing rate of TEOAE was 64.0% in the tinnitus group 1, 91.3% in the group 2, and 100% in the control group (group 1 P < 0.01, group 2 P >0.05 ). (2) The passing rate of DPOAE was 100% in three groups. But comparing to the control group, the amplitudes of DPOAE at the limited frequency ranges (3.125 kHz and 8.837 kHz) of the tinnitus group 1 was significant decreased ( P <0.05). (3) The subjective tinnitus frequencies were 0.25 approximately 8.00 kHz. The decreases in amplitudes and absent within the tinnitus frequencies were observed in TEOAE and DPOAE audiogram. CONCLUSION: Some patients of normal hearing with tinnitus have had early harmness of outer hair cell in cochlear. Evoked otoacoustic emissions is one of worthy methods to evaluated objectively the tinnitus. TEOAE is more susceptible to harmness in cochlear than DPOAE. DPOAE is superior to the analysis of tinnitus frequencies.

[Extraluminal foreign body originated from pharynx and esophagus (24 cases report)].

OBJECTIVE: To summarize the symptoms, various diagnostic procedures, and therapy of extraluminal foreign body originated from pharynx and esophagus (EFBOPE). METHOD: Twenty-four patients with EFBOPE were retrospectively reviewed. RESULT: Twenty-two cases were removed surgically, 1 case was spontaneous expulsion, 1 case died. CONCLUSION: EFBOPE is seldom seen in the clinical, diagnosis of EFBOPE should be considered whenever haematemesis or haemorrhage, inflammation or abscess in parapharyngeal space outside of pharynx and esophagus are presented after ingesting foreign body. Radiography and computed tomography are main diagnostic tools. Surgical treatment is the only effective method for EFBOPE and must be performed in time.

[Comprehensive evaluation of the middle ear function in children with secretory otitis media after tympanotomy tube insertion].

OBJECTIVE: To study the method on comprehensive evaluation of the middle ear function in children with secretory otitis media (SOM) after tympanotomy tube insertion. METHOD: Ear canal volume (ECV), pure tone audiometry and distortion product otoacoustic emission(DPOAE) were carried out in 31 children(43 ears) with SOM before and 1 month after tube insertion,in the meantime Eustachian tube function was recorded. The tympanotomy tube was observed under microscope. RESULT: After one month of tube insertion, the hearing level was improved in 39 ears with an ECV > 2.0 ml. In addition,the detection rate and amplitude of DPOAE were significantly increased in these 39 ears. No case of the function of Eustachian tube was complete recovered. CONCLUSION: ECV, pure tone audiometry, DPOAE and inflation-deflation test are significantly clinical worth for comprehensive evaluation of the middle ear function in children with SOM after tympanotomy tube insertion.