1.Geraniin attenuates isoproterenol-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis
Jiaqi DING ; Shenjie ZHANG ; Qi LI ; Boyu XIA ; Jingjing WU ; Xu LU ; Chao HUANG ; Xiaomei YUAN ; Qingsheng YOU
The Korean Journal of Physiology and Pharmacology 2025;29(3):307-319
Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.
2.Natural product virtual-interact-phenotypic target characterization:A novel approach demonstrated with Salvia miltiorrhiza extract
Rui XU ; Hengyuan YU ; Yichen WANG ; Boyu LI ; Yong CHEN ; Xuesong LIU ; Tengfei XU
Journal of Pharmaceutical Analysis 2025;15(2):425-441
Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the present study,an innovative natural product virtual screening-interaction-phenotype(NP-VIP)strategy that integrates virtual screening,chemical proteomics,and metabolomics to identify and validate the bioactive targets of NPs.This approach reduces false positive results and enhances the ef-ficiency of target identification.Salvia miltiorrhiza(SM),a herb with recognized therapeutic potential against ischemic stroke(IS),was used to illustrate the workflow.Utilizing virtual screening,chemical proteomics,and metabolomics,potential therapeutic targets for SM in the IS treatment were identified,totaling 29,100,and 78,respectively.Further analysis via the NP-VIP strategy highlighted five high-confidence targets,including poly[ADP-ribose]polymerase 1(PARP1),signal transducer and activator of transcription 3(STAT3),amyloid precursor protein(APP),glutamate-ammonia ligase(GLUL),and glutamate decarboxylase 67(GAD67).These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM.The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research,proposing a comprehensive approach that could be adapted for broader pharmacological explorations.
3.Efficacy and safety of TACE combined with lenvatinib and PD-1 inhiti-bors in the treatment of hepatocellular carcinoma with portal vein tumor thrombus
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(5):648-656
AIM:To investigate the efficacy and safety of TACE combined with lenvatinib and PD-1 inhitibors for hepatocellular carcinoma(HCC)with portal vein tumor thrombus(PVTT).METHO DS:HCC patients with PVTT who received TACE combined with lenvatinib and PD-1 inhitibors as first-line ther-apy in clinical practice were included in this study retrospectively.Therapeutic outcomes of this regi-men were calculated based on the target lesions evaluated using mRECIST criteria.Additionally,all the subjects were followed up regularly to obtain the prognostic outcomes.Safety profile observed during the combination therapy was collected and documented specifically.Log-rank test was used for exploratory analysis between prognosis and base-line characteristics,and Cox regression analysis was adopted for multivariate analysis.RESULTS:A total of 67 HCC patients with PVTT who received TACE combined with lenvatinib and PD-1 inhitibors were included in this study ultimately,4 patients achieved complete response,30 patients were par-tial response,25 patients were stable disease,5 pa-tients were disease progression and 3 patients were not available for the response outcomes.Therefore,the objective response rate(ORR)of this regimen was 50.7%and disease control rate(DCR)was 88.1%.Prognostic data suggested that the me-dian progression free survival(PFS)of the 67 HCC patients with PVTT was 9.3 months(95%CI:5.85-12.75),and the median overall survival(OS)was 24.4 months(95%CI:19.11-29.69).Safety profile highlighted that a total of 65 patients experienced adverse reactions regardless of grade when re-ceived TACE combined with lenvatinib and PD-1 in-hitibors(97.0%),among whom,a total of 34 pa-tients were deemed as grade ≥3 adverse reactions(50.7%).The most common adverse reactions were hypertension,fatigue,abnormal liver function,nau-sea and vomiting and diarrhea.CONCLUSION:TACE combined with lenvatinib and PD-1 inhitibors as first-line therapy for HCC with PVTT demonstrated encouraging efficacy and acceptable safety profile.
4.Geraniin attenuates isoproterenol-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis
Jiaqi DING ; Shenjie ZHANG ; Qi LI ; Boyu XIA ; Jingjing WU ; Xu LU ; Chao HUANG ; Xiaomei YUAN ; Qingsheng YOU
The Korean Journal of Physiology and Pharmacology 2025;29(3):307-319
Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.
5.Geraniin attenuates isoproterenol-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis
Jiaqi DING ; Shenjie ZHANG ; Qi LI ; Boyu XIA ; Jingjing WU ; Xu LU ; Chao HUANG ; Xiaomei YUAN ; Qingsheng YOU
The Korean Journal of Physiology and Pharmacology 2025;29(3):307-319
Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.
6.Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract.
Rui XU ; Hengyuan YU ; Yichen WANG ; Boyu LI ; Yong CHEN ; Xuesong LIU ; Tengfei XU
Journal of Pharmaceutical Analysis 2025;15(2):101101-101101
Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.
7.Geraniin attenuates isoproterenol-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis
Jiaqi DING ; Shenjie ZHANG ; Qi LI ; Boyu XIA ; Jingjing WU ; Xu LU ; Chao HUANG ; Xiaomei YUAN ; Qingsheng YOU
The Korean Journal of Physiology and Pharmacology 2025;29(3):307-319
Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.
8.Geraniin attenuates isoproterenol-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis
Jiaqi DING ; Shenjie ZHANG ; Qi LI ; Boyu XIA ; Jingjing WU ; Xu LU ; Chao HUANG ; Xiaomei YUAN ; Qingsheng YOU
The Korean Journal of Physiology and Pharmacology 2025;29(3):307-319
Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.
9.Research on the prevention of urinary tract infection in patients with BPH after TURP by Wenpi Yishen method
Jingcheng LYU ; Fengbo ZHANG ; Dongyue WU ; Hai LIN ; Shuai XU ; Boyu YANG
International Journal of Surgery 2025;52(6):397-402
Objective:To explore whether the Wenpi Yishen method can effectively prevent the occurrence of urinary tract infection after transurethral resection of the prostate (TURP) in patients with benign prostatic hyperplasia (BPH).Methods:A prospective randomized controlled study was conducted on 173 patients with BPH admitted to Beijing Friendship Hospital, Capital Medical University from January 2023 to December 2024, and they were divided into the control group ( n=104) and the Wenpi Yishen group ( n=69) by the random number table method. Patients in the control group were treated only with conventional methods after TURP, while patients in the Wenpi Yishen group were treated with the Wenpi Yishen method in addition to the conventional treatment after TURP to prevent urinary tract infections. The preoperative general data such as age and body mass index of the two groups of patients were compared, as well as the traditional chinese medical syndrome scores before and after TURP, international prostate symptom scores (IPSS), self-rating anxiety scale (SAS) scores, urinary tract infections and postoperative complications, etc. Measurement data were expressed as mean±standard deviation ( ± s), and t-test was used for comparison between groups; count data were expressed as the cases and percentage, and Chi-square test was used for comparison between groups. Results:There were no statistically significant differences between the two groups of patients in terms of preoperative traditional chinese medical syndrome scores, IPSS scores, SAS scores, and inflammation-related indicators ( P>0.05). In the patients of control group, 44 cases (42.3%) had positive urine cultures before the operation, there was 28 cases (40.6%) in the Wenpi Yishen group, and the difference was no statistically significant ( P>0.05). In the patients of control group, 28 cases showed positive urine cultures within one month after TURP, among which 9 cases were new-onset urinary tract infections, there was 9 cases in the Wenpi Yishen group, and no new-onset urinary tract infections, and the differences were statistically significant ( P<0.05). The traditional chinese medical syndrome scores of patients in the control group and Wenpi Yishen group after surgery were (8.0±2.1) points and (6.9±2.4) points, respectively, and the therapeutic rates of syndromes were (60.2±10.0)% and (65.2±12.2)%, respectively, the differences were statistically significant ( P<0.05). The IPSS score and SAS score of patients in the Wenpi Yishen group decreased by (21.0±4.5) points and (14.7±2.9) points before and after TURP, respectively, which were both lower than those of the control group [(19.1±3.5) points and (11.7±3.7) points], and the differences were statistically significant ( P<0.05). In terms of the severity of postoperative complications, 34 cases (32.7%) in the control group had relatively severe complications such as urinary tract infection and hematuria, while only 5 cases (7.25%) in the Wenpi Yishen group, and the difference was statistically significant ( P<0.05). However, there was no statistically significant difference in the postoperative inflammation-related indicators between the two groups ( P>0.05). Conclusion:For patients with BPH, early application of the Wenpi Yishen method after TURP can effectively prevent the occurrence of urinary tract infections, and improve the uncomfortable symptoms in the short term after the operation, as well as relieve the generation of anxiety.
10.Efficacy and safety of TACE combined with lenvatinib and PD-1 inhiti-bors in the treatment of hepatocellular carcinoma with portal vein tumor thrombus
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(5):648-656
AIM:To investigate the efficacy and safety of TACE combined with lenvatinib and PD-1 inhitibors for hepatocellular carcinoma(HCC)with portal vein tumor thrombus(PVTT).METHO DS:HCC patients with PVTT who received TACE combined with lenvatinib and PD-1 inhitibors as first-line ther-apy in clinical practice were included in this study retrospectively.Therapeutic outcomes of this regi-men were calculated based on the target lesions evaluated using mRECIST criteria.Additionally,all the subjects were followed up regularly to obtain the prognostic outcomes.Safety profile observed during the combination therapy was collected and documented specifically.Log-rank test was used for exploratory analysis between prognosis and base-line characteristics,and Cox regression analysis was adopted for multivariate analysis.RESULTS:A total of 67 HCC patients with PVTT who received TACE combined with lenvatinib and PD-1 inhitibors were included in this study ultimately,4 patients achieved complete response,30 patients were par-tial response,25 patients were stable disease,5 pa-tients were disease progression and 3 patients were not available for the response outcomes.Therefore,the objective response rate(ORR)of this regimen was 50.7%and disease control rate(DCR)was 88.1%.Prognostic data suggested that the me-dian progression free survival(PFS)of the 67 HCC patients with PVTT was 9.3 months(95%CI:5.85-12.75),and the median overall survival(OS)was 24.4 months(95%CI:19.11-29.69).Safety profile highlighted that a total of 65 patients experienced adverse reactions regardless of grade when re-ceived TACE combined with lenvatinib and PD-1 in-hitibors(97.0%),among whom,a total of 34 pa-tients were deemed as grade ≥3 adverse reactions(50.7%).The most common adverse reactions were hypertension,fatigue,abnormal liver function,nau-sea and vomiting and diarrhea.CONCLUSION:TACE combined with lenvatinib and PD-1 inhitibors as first-line therapy for HCC with PVTT demonstrated encouraging efficacy and acceptable safety profile.

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