Oyewusi Habeebat Adekilekun, Oladipo Oluwatosin Olubunmi, Muritala Hamdalat Folake, Olaleye Abike Christianah, Akinyede Kolajo Adedamola
Biochemistry unit, Department of Science Technology, The Federal Polytechnic, P.M.B 5351, Ado Ekiti, Ekiti State, Nigeria.
Microbiology unit, Department of Science Technology, The Federal Polytechnic, P.M.B 5351, Ado Ekiti, Ekiti State, Nigeria.
Int J Biol Macromol. 2024 Dec;283(Pt 2):137513. doi: 10.1016/j.ijbiomac.2024.137513. Epub 2024 Nov 16.
The study uses in-vitro antioxidant, ex-vivo enzyme kinetics and in-silico approach using standard protocols to understand their inhibitory mechanism better. The study revealed that bacterial strain HOKA1 isolated from Oniru beach, grown in nutrient agar supplemented with sodium chloride (30%NaCl). Moreso, the bacterial strain HOKA1 extract showed better antioxidant capability and greatly reduced the penile and cardiac cGMP with the highest penile and cardiac concentration between 0.013 and 0.183 μM/Min as compared to the sildenafil citrate (0.00-0.203 μM/Min). Moreover, the kinetic parameters (V and K) effects revealed that bacterial strain HOKA1 extract inhibited PDE-5 activities better than sildenafil citrate. The GC-MS analysis revealed twenty-nine bioactive compounds in the extract, and these compounds could provide comprehensible supporting evidence for the antioxidant and inhibitory potential of the strain HOKA1 extract on PDE-5 activity. Molecular docking study revealed majority of the GC-MS-identified bioactive constituents from the HOKA1 extract showed high binding energy or lower bonding affinities (-6.8 to -3.3 kcal/mol) compared to reference drug sildenafil citrate (-9.6 kcal/mol), except campesterol (-10.0 kcal/mol); also, ergostane (-9.9 kcal/mol). The results of 100 ns simulation (RMSF, RMSD, Rg and H-bond) show extraordinary stability of PDE-5 with campesterol and ergostane, so also complimentary binding energy of MM-PBSA (campesterol -65.92±4.09 kcal/mol; ergostane -57.23±4.70 kcal/mol) indicating their probability of acting promising PDE-5 inhibitors. Therefore, the study revealed that bacterial strain HOKA1 extract showed a better aphrodisiac property, and its bioactive compounds (campesterol and ergostane) should be considered in upcoming rational development and design of more active selective PDE-5 inhibitors, making a treatment for erectile dysfunction.
该研究采用体外抗氧化、离体酶动力学以及基于标准方案的计算机模拟方法，以更好地理解其抑制机制。研究表明，从奥尼鲁海滩分离出的细菌菌株HOKA1，在添加氯化钠（30%NaCl）的营养琼脂中生长。此外，细菌菌株HOKA1提取物显示出更好的抗氧化能力，与枸橼酸西地那非（0.00 - 0.203μM/分钟）相比，能极大地降低阴茎和心脏中的环磷酸鸟苷（cGMP），阴茎和心脏中的最高浓度在0.013至0.183μM/分钟之间。而且，动力学参数（V和K）效应表明，细菌菌株HOKA1提取物比枸橼酸西地那非更能有效抑制磷酸二酯酶5（PDE - 5）的活性。气相色谱 - 质谱联用（GC - MS）分析显示提取物中含有29种生物活性化合物，这些化合物可为菌株HOKA1提取物对PDE - 5活性的抗氧化和抑制潜力提供有力的支持证据。分子对接研究表明，与参考药物枸橼酸西地那非（-9.6 kcal/mol）相比，HOKA1提取物中大多数经GC - MS鉴定的生物活性成分显示出较高的结合能或较低的结合亲和力（-6.8至-3.3 kcal/mol），除了菜油甾醇（-10.0 kcal/mol）；还有麦角甾烷（-9.9 kcal/mol）。100纳秒模拟（均方根波动、均方根偏差、回旋半径和氢键）的结果表明，PDE - 5与菜油甾醇和麦角甾烷具有非凡的稳定性，同时MM - PBSA的互补结合能（菜油甾醇 - 65.92±4.09 kcal/mol；麦角甾烷 - 57.23±4.70 kcal/mol）表明它们有可能成为有前景的PDE - 5抑制剂。因此，该研究表明细菌菌株HOKA1提取物具有更好的壮阳特性，其生物活性化合物（菜油甾醇和麦角甾烷）应在未来更具活性的选择性PDE - 5抑制剂的合理开发和设计中予以考虑，用于治疗勃起功能障碍。
