Deeh Patrick Brice Defo, Kim Hye-Yong, Han Kiseok, Sathiyaseelan Anbazhagan, Cho Hyun-Jong, Wang Myeong-Hyeon
Department of Bio-Health Convergence, Kangwon National University, Chuncheon 24341, Republic of Korea.
Department of Dental Hygiene, College of Health Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
Pharmaceuticals (Basel). 2025 May 27;18(6):803. doi: 10.3390/ph18060803.
: Cyclophosphamide (CP) chemotherapy is commonly associated with various side effects. The development of an effective therapy capable of counteracting these effects is of great interest. : We evaluated the effects of a novel polyherbal formulation (PHF) on CP cytotoxicity in TM3 cells and fictive ejaculation in rats, and determined its possible mechanism. : The phytochemical analysis of PHF was determined by GC-MS. Various oxidative stress-related parameters (DPPH, ABTS, CUPRAC, FRAP, MMP, and DCF-DA) and the cytotoxicity (hemolysis and HET-CAM) of PHF were evaluated. Its effect on fictive ejaculation was tested by recording the electromyographic activities of bulbospongiosus muscles, and the involvement of TRPV1/TRPM2 channels was investigated using their specific agonists and antagonists. : We found that PHF contained various phytocompounds. PHF prevented CP-induced oxidative stress in TM3 cells, probably due to its strong antioxidant potential. For instance, PHF inhibited apoptosis, lipid peroxidation, and ROS generation. Furthermore, the activities of capsaicin (CAP) and cumene hydroperoxide (CHPx) were significantly lowered by PHF, indicating TRPV1 and TRPM2 inhibition. In the in vivo study conducted in spinal male rats, the number of contractions of the bulbospongiosus muscles was significantly ( < 0.001) lowered in the PHF + DOPA (1.54 ± 0.3) and PHF + CAP (2.43 ± 0.74) groups, compared with the DOPA (8.75 ± 0.71) and CAP (7.41 ± 1.01) groups, respectively. Additionally, PHF delayed the pro-ejaculatory effects of dopamine (by 17.6%) and capsaicin (by 32.69%). The in silico study revealed a strong binding affinity between the selected PHF phytocompounds and the active pockets of TRPV1 and TRPM2. HET-CAM and hemolysis assays revealed no harmful effects of PHF. : PHF prevented CP cytotoxicity in TM3 cells and delayed the pro-ejaculatory effects of dopamine and capsaicin in spinal rats through dopamine and TRPV1 inhibition. PHF could be a potential candidate for the management of CP chemotherapy-related disorders, such as premature ejaculation, in particular.
环磷酰胺（CP）化疗通常会伴随各种副作用。开发一种能够对抗这些副作用的有效疗法备受关注。
我们评估了一种新型多草药配方（PHF）对TM3细胞中CP细胞毒性以及大鼠假射精的影响，并确定了其可能的作用机制。
通过气相色谱 - 质谱联用（GC - MS）对PHF进行植物化学分析。评估了PHF的各种氧化应激相关参数（DPPH、ABTS、CUPRAC、FRAP、MMP和DCF - DA）以及细胞毒性（溶血和鸡胚绒毛尿囊膜试验）。通过记录球海绵体肌的肌电图活动来测试其对假射精的影响，并使用TRPV1/TRPM2通道的特异性激动剂和拮抗剂来研究其参与情况。
我们发现PHF含有多种植物化合物。PHF可预防CP诱导的TM3细胞氧化应激，这可能归因于其强大的抗氧化潜力。例如，PHF可抑制细胞凋亡、脂质过氧化和活性氧生成。此外，PHF可显著降低辣椒素（CAP）和氢过氧化异丙苯（CHPx）的活性，表明其对TRPV1和TRPM2有抑制作用。在对脊髓损伤雄性大鼠进行的体内研究中，与多巴胺组（8.75±0.71）和辣椒素组（7.41±1.01）相比，PHF + 多巴胺（1.54±0.3）组和PHF + 辣椒素（2.43±0.74）组球海绵体肌的收缩次数显著降低（<0.001）。此外，PHF可延迟多巴胺（延迟17.6%）和辣椒素（延迟32.69%）的促射精作用。计算机模拟研究表明，所选的PHF植物化合物与TRPV1和TRPM2的活性口袋之间具有很强的结合亲和力。鸡胚绒毛尿囊膜试验和溶血试验表明PHF无有害影响。
PHF可预防TM3细胞中的CP细胞毒性，并通过抑制多巴胺和TRPV1来延迟脊髓损伤大鼠中多巴胺和辣椒素的促射精作用。PHF尤其可能是治疗与CP化疗相关疾病（如早泄）的潜在候选药物。
