1.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
2.Identification of Alumen and Ammonium alum Based on XRD, FTIR, TG-DTA Combined with Chemometrics
Bin WANG ; Jingwei ZHOU ; Huangsheng ZHANG ; Jian FENG ; Hanxi LI ; Guorong MEI ; Jiaquan JIANG ; Hongping CHEN ; Fu WANG ; Yuan HU ; Youping LIU ; Shilin CHEN ; Lin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):178-186
ObjectiveTo establish the multi-technique characteristic profiles of Alumen by X-ray diffraction(XRD), Fourier-transform infrared spectroscopy(FTIR) and thermogravimetric-differential thermal analysis(TG-DTA), and to explore the spectral characteristics for rapid identification of Alumen and its potential adulterant, Ammonium alum. MethodsA total of 27 batches of Alumen samples from 8 production regions were collected for preliminary identification based on visual characteristics. The PDF standard cards of XRD were used to differentiate Alumen from A. alum, and the XRD characteristic profiles of Alumen were established, and then the common peaks were screened. Based on hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), the characteristic information that could be used for identification of Alumen was selected with variable importance in the projection(VIP) value>1. FTIR characteristic profiles of Alumen were established, and key wavenumbers for identification were screened by HCA and OPLS-DA with VIP value>1. Meanwhile, the thermogravimetric differences between Alumen and A. alum were analyzed by TG-DTA, and the thermogravimetric traits that could be used for identification were screened. ResultsAlumen and A. alum could not be effectively distinguished by traits alone. However, by comparing the PDF standard cards of XRD, 15 batches of Alumen and 12 batches of A. alum could be distinguished. In the XRD profiles, 10 characteristic peaks were confirmed, corresponding to diffraction angles of 14.560°, 24.316°, 12.620°, 32.122°, 17.898°, 34.642°, 27.496°, 46.048°, 40.697° and 21.973°. In the FTIR profiles, 4 wavenumber ranges(399.193-403.050, 1 186.010-1 471.420, 1 801.190-2 620.790, 3 612.020-3 997.710 cm-1) and 12 characteristic wavenumbers(1 428.994, 1 430.922, 1 432.851, 1 434.779, 1 436.708, 1 438.636, 1 440.565, 1 442.493, 1 444.422, 1 446.350, 1 448.279, 1 450.207 cm-1) were identified. In the TG-DTA profiles, there were characteristic decomposition peaks of ammonium ion and mass reduction features near 555.34 ℃ for A. alum. These characteristics could serve as important criteria for distinguishing the authenticity of Alumen. ConclusionXRD, FTIR and TG-DTA can be used to rapidly detect Alumen and A. alum, and combined with the discriminant features selected through chemometrics, the rapid and accurate identification of Alumen and A. alum can be achieved. The research findings provide new approaches for the rapid identification of Alumen.
3.Identification of Alumen and Ammonium alum Based on XRD, FTIR, TG-DTA Combined with Chemometrics
Bin WANG ; Jingwei ZHOU ; Huangsheng ZHANG ; Jian FENG ; Hanxi LI ; Guorong MEI ; Jiaquan JIANG ; Hongping CHEN ; Fu WANG ; Yuan HU ; Youping LIU ; Shilin CHEN ; Lin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):178-186
ObjectiveTo establish the multi-technique characteristic profiles of Alumen by X-ray diffraction(XRD), Fourier-transform infrared spectroscopy(FTIR) and thermogravimetric-differential thermal analysis(TG-DTA), and to explore the spectral characteristics for rapid identification of Alumen and its potential adulterant, Ammonium alum. MethodsA total of 27 batches of Alumen samples from 8 production regions were collected for preliminary identification based on visual characteristics. The PDF standard cards of XRD were used to differentiate Alumen from A. alum, and the XRD characteristic profiles of Alumen were established, and then the common peaks were screened. Based on hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), the characteristic information that could be used for identification of Alumen was selected with variable importance in the projection(VIP) value>1. FTIR characteristic profiles of Alumen were established, and key wavenumbers for identification were screened by HCA and OPLS-DA with VIP value>1. Meanwhile, the thermogravimetric differences between Alumen and A. alum were analyzed by TG-DTA, and the thermogravimetric traits that could be used for identification were screened. ResultsAlumen and A. alum could not be effectively distinguished by traits alone. However, by comparing the PDF standard cards of XRD, 15 batches of Alumen and 12 batches of A. alum could be distinguished. In the XRD profiles, 10 characteristic peaks were confirmed, corresponding to diffraction angles of 14.560°, 24.316°, 12.620°, 32.122°, 17.898°, 34.642°, 27.496°, 46.048°, 40.697° and 21.973°. In the FTIR profiles, 4 wavenumber ranges(399.193-403.050, 1 186.010-1 471.420, 1 801.190-2 620.790, 3 612.020-3 997.710 cm-1) and 12 characteristic wavenumbers(1 428.994, 1 430.922, 1 432.851, 1 434.779, 1 436.708, 1 438.636, 1 440.565, 1 442.493, 1 444.422, 1 446.350, 1 448.279, 1 450.207 cm-1) were identified. In the TG-DTA profiles, there were characteristic decomposition peaks of ammonium ion and mass reduction features near 555.34 ℃ for A. alum. These characteristics could serve as important criteria for distinguishing the authenticity of Alumen. ConclusionXRD, FTIR and TG-DTA can be used to rapidly detect Alumen and A. alum, and combined with the discriminant features selected through chemometrics, the rapid and accurate identification of Alumen and A. alum can be achieved. The research findings provide new approaches for the rapid identification of Alumen.
4.Evaluation of myopia prevention and control effect of defocus incorporated multiple segments lenses in children with monocular myopia
Lu JIANG ; Mengling PENG ; Miao MA ; Xue YUAN ; Chao ZHOU
International Eye Science 2025;25(10):1683-1687
AIM:To compare the changes in diopters and axial length after 1 a of wearing defocus incorporated multiple segments(DIMS)lenses or single vision(SV)spectacle lenses in children with monocular myopia.METHODS:In this retrospective case group study, monocular myopia children aged from 6 to 14 years old in Hankou Aier Eye Hospital from October 2020 to October 2022, who were fitted with DIMS lens(n=52)or single-vision(SV)spectacle lenses(n=49)were collected. The spherical degree of myopia eyes ranged from -4.00 D to -0.50 D and the nonmyopic eyes ranged from 0 to +1.00 D, astigmatism in all eyes ranged from 0 to -2.00 D. The DIMS lens group was classified into DIMS-myopia group(the myopic eyes)and DIMS-nonmyopia group(the nonmyopic eyes). The SV lens group was also divided into SV-myopia group and SV-nonmyopia group. The changes in spherical equivalent refraction(SER)and axial length(AL)of each group were compare before and after wearing lenses for 1 a, and variations in SER and AL of both eye among groups were analzed.RESULTS: After wearing lenses for 1 a, the changes of SER in the DIMS-myopic group and the DIMS-nonmyopic group were -0.41±0.44 and -0.26±0.54 D, respectively, and the changes of AL were 0.18±0.20 and 0.15±0.15 mm, respectively. SER changes were -0.74±0.63 and -0.70±0.68 D in SV-myopic group and SV-nonmyopic group, and AL changes were 0.30±0.28 and 0.31±0.28 mm. The changes of SER and AL in the DMS-myopic and non-myopic groups were slower than those in SV group(all P<0.05). Compared with SV lenses, wearing DIMS lenses delayed and 44.6% in myopia eyes, and 62.9% in non-myopia eyes, AL delayed by 40.0% in myopia eyes and 51.6% in non-myopia eyes. The percentage of 1-year AL change ≤0.2 mm in the DIMS-myopic group and non-myopic group was 53.9% and 65.4%, respectively, which was higher than that in the SV myopic group(34.7% and 42.9%, all P<0.05). The percentage of AL change >0.4 mm in the DIMS-myopic group and nonmyopic group was 17.3% and 7.7%, respectively, which was lower than that in the SV myopic group(32.7% and 28.6%, all P<0.05). There was no significant correlation between the change of AL and age and baseline AL in the DIMS-myopic and non-myopic groups after wearing lens for 1 a(all P>0.05); the change of AL in SV-myopic group and non-myopic group was negatively correlated with age(r=-0.446, P=0.001; r=-0.312, P=0.029), and there was no significant correlation with baseline AL(all P>0.05).CONCLUSION: DIMS lens has a good effect on myopia control and prevention in both myopia and non-myopia children with monocular myopia. Children with early pre-myopia can wear DIMS to prevent myopia.
5.Pathogenesis and Differentiated Treatment Strategies of Childhood Tic Disorders Based on WANG Xugao's “Thirty Methods of Treating the Liver”
Rui ZHAI ; Juan DUAN ; Yuan LI ; Yanlin JIANG ; Congxiao ZHOU ; Zhenhua YUAN ; Da LI ; Junhong WANG
Journal of Traditional Chinese Medicine 2024;65(2):149-153
Based on WANG Xugao's “thirty methods of treating the liver”, it is believed that the occurrence and development of childhood tic disorders follow the dynamic progression from liver qi disease to liver fire disease and then liver wind disease. The basic pathogenesis of three stages are characterized by binding constraint of liver qi, liver fire hyperactivity, and internal stirring of liver wind. Moreover, liver-blood deficiency and stagnation, and malnutrition of liver yin as the main point in terms of the imbalance of liver qi, blood, yin, and yang should be considered, as well as the imbalance relationship of the five zang organs such as the involvement of other organs and the gradually reach of the other organs. Guided by the principles of “thirty methods of treating the liver”, the treatment of tic disorders in liver qi stage should focus on soothing the liver and rectifying qi, soothing the liver and unblocking the collaterals, using Xiaochaihu Decoction (小柴胡汤) and Sini Powder (四逆散). The treatment of tic disorders in liver fire stage involves clearing, draining and resolving liver heat, using Longdan Xiegan Decoction (龙胆泻肝汤), Xieqing Pill (泻青丸), Danggui Longhui Pill (当归龙荟丸), and Huagan Decoction (化肝煎). The treatment of tic disorders in liver wind stage involves extinguishing wind and subduing yang, using Lingjiao Gouteng Decoction (羚角钩藤汤) and Liuwei Dihuang Pill (六味地黄丸). Throughout the treatment process, attention should be paid to harmonizing the liver's qi, blood, yin, and yang, as well as addressing the pathology of other organs.
6.Fitting Degrees of Animal Models of Diarrhea-irritable Bowel Syndrome with Clinical Characteristics of Western Medicine and Traditional Chinese Medicine
Fengru JIANG ; Youcheng HE ; Yue WU ; Keyi PAN ; Chunyu ZHOU ; Shuyu CAI ; Jianye YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):218-227
Diarrhea-irritable bowel syndrome (IBS-D) is one of the common functional bowel diseases in clinical practice. Since it pathogenesis is complex and has not been fully elucidated, effective treatment methods remains to be developed for this disease. Establishing the animal models of IBS-D in accordance with the clinical characteristics of traditional Chinese medicine (TCM) and Western medicine helps to reveal the pathogenesis of this disease and improve the treatment plan. The fitting degree of an animal model with clinical characteristics is an indicator to evaluate the effectiveness of the animal model in simulating the disease characteristics of Western medicine and the syndromes of TCM based on the latest diagnostic standards. By reviewing the relevant articles about the animal models of IBS-D, we discovered that rats were the preferred animals for modeling, and the models were mainly induced by single factors, double factors, or the combination of multiple factors. The established animal models mainly present symptoms or signs associated with visceral hypersensitivity or/and gastrointestinal motility abnormalities. The single factor-induced rat models of IBS-D had high fitting degrees with the clinical characteristics of Western medicine but low fitting degrees with the TCM syndromes. The animal models induced by two or more factors had high but varied fitting degrees with the clinical characteristics of Western medicine. In addition, the animal models of IBS-D considering TCM syndromes mainly focuses on the syndrome of liver depression and spleen deficiency, and few models were established for the syndromes of spleen-kidney Yang deficiency, spleen-stomach dampness-heat, spleen deficiency and dampness excess, and cold and heat in complexity. Therefore, it is essential to improve the existing or develop new animal models of IBS-D in the future, so as to provide more tools for deciphering the mechanisms of TCM and Western medicine and developing treatment methods for this disease.
7.Optimization of Extraction and Purification Process of Total Phenols from Deoiled Cinnamomum Longepaniculatum Leaves and Its Antioxidant Study in Vitro
Xi ZHOU ; Yu JIANG ; Yefei YUAN
Chinese Journal of Modern Applied Pharmacy 2024;41(11):1499-1507
OBJECTIVE
To explore the optimal process of extraction and purification of total phenols from deoiled Cinnamomum longepaniculatum leaves, and to evaluate the antioxidant activity in vitro before and after purification, so as to provide a theoretical basis for rational development and utilization of Cinnamomum longepaniculatum.
METHODS
The L18(37) orthogonal experiment was carried out on the basis of five-single factor and three-level experiments, such as concentration of ethanol(A), ratio of liquid-material(B), extraction temperature(C), extraction time(D), and extraction times(E). The extraction process of total phenols was optimized, by taking the amount of total phenols extraction as the process investigation index. Taking the adsorption and desorption performance under dynamic and static conditions as the investigation index of total phenols purification process, the purification process of total phenols was optimized by macroporous resin. With vitamin C(Vc) as the positive control, the antioxidant activity in vitro of total phenols before and after purification were evaluated by DPPH radical scavenging, ABTS+ radical scavenging and determination of total reducing capacity.
RESULTS
The best extraction technology conditions of total phenols were as follows: ratio of liquid-material 30 mL·g−1, concentration of ethanol 50%, extraction time 2 h, extraction temperature 90 ℃, extraction 2 times. Under such conditions , the extraction amount of total phenols from deoiled Cinnamomum longepaniculatum leaves was 15.63 mL·g−1. HPD-600 type macroporous resin showed the best purifying profile. The best purification technology conditions were as follows: the concentration of sample solution was 0.5 g·L−1, the sample solution pH value was 3, the sample volume was 2.5 BV, the sample flow rate 1 mL·min−1, the impurity was removed by 4.5 BV distilled water, the elution concentration of ethanol was 60%, the eluate pH value 7, the elution flow rate 1 mL·min−1, 4.5 BV eluent was collected and the total phenols assay was increased from 12.51% to 26.40%. The purified total phenols showed excellent antioxidant activity in vitro. The scavenging effect of total phenols after purification on DPPH and ABTS+ free radicals increased with the increase of total phenols concentration. The IC50 values of DPPH radical scavenging activity of total phenols before and after purification were (68.31±1.96)mg·L−1 and (38.07±0.66)mg·L−1, respectively. The IC50 values of ABTS+ radical scavenging activity of total phenols before and after purification were (23.88±1.66)mg·L−1and (14.28±0.19)mg·L−1, respectively. The absorbance values of the total reducing capacity of total phenols was 1.68 times higher than that before purification. The scavenging effect of total phenols before and after purification on DPPH, ABTS+ free radical scavenging and total reducing capacity was weaker than that of Vc.
CONCLUSION
The process is stable and feasible, suitable for industrial production, and has the advantages of simplicity, rapidity and accuracy, which lays a foundation for further research on Cinnamomum longepaniculatum and the development of natural antioxidants.
8.The relationship between activities of daily living and mental health in community elderly people and the mediating role of sleep quality
Heng-Yi ZHOU ; Jing LI ; Dan-Hua DAI ; Yang LI ; Bin ZHANG ; Rong DU ; Rui-Long WU ; Jia-Yan JIANG ; Yuan-Man WEI ; Jing-Rong GAO ; Qi ZHAO
Fudan University Journal of Medical Sciences 2024;51(2):143-150
Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P<0.001;r=0.466,P<0.001);ADL was positively correlated with sleep quality(r=0.294,P<0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P<0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.
9.Application Study of Enzyme Inhibitors and Their Conformational Optimization in The Treatment of Alzheimer’s Disease
Chao-Yang CHU ; Biao XIAO ; Jiang-Hui SHAN ; Shi-Yu CHEN ; Chu-Xia ZHANG ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Zhi-Cheng LIN ; Kai XIE ; Shu-Jun XU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2024;51(7):1510-1529
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.
10.Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation
Tingting YANG ; Jiayu YUAN ; Yuting PENG ; Jiale PANG ; Zhen QIU ; Shangxiu CHEN ; Yuhan HUANG ; Zhenzhou JIANG ; Yilin FAN ; Junjie LIU ; Tao WANG ; Xueyan ZHOU ; Sitong QIAN ; Jinfang SONG ; Yi XU ; Qian LU ; Xiaoxing YIN
Journal of Pharmaceutical Analysis 2024;14(1):52-68
The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.


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