Contraceptive potential of Andrographis paniculata is via androgen suppression and not induction of oxidative stress in male Wistar rats

Ogundola, Adijat Funke; Akhigbe, R.E.; Saka, W.A.; Adeniyi, A.O.; Adeshina, Olamilekan Sultan; Babalola, D.O.; Akhigbe, T. M.

doi:10.1016/j.tice.2021.101632

Cited by 13 publications

(9 citation statements)

References 35 publications

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“…Each measurement was taken by two experts who were blinded to the study protocol. The mean value obtained for each testis was used as the measurement for that testis [31,32].…”

Section: Assessment Of Testicularmentioning

confidence: 99%

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Proton Pump Dysfunction and Upregulation of Caspase-3 Activity via Oxidative-Sensitive Signaling Mediate Rohypnol-Induced Testicular Toxicity

et al. 2023

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Rohypnol is a benzodiazepine that is used for its anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties, but commonly abused. It has been reported to induce sexual dysfunction; however, its effect on testicular integrity and sperm quality is yet to be documented. This study evaluated the impact of Rohypnol on testicular integrity, circulatory testosterone, spermatogenesis, and sperm quality. The likely role of oxidative stress-dependent pathway as well as testicular proton pumps and caspase-3 activity in Rohypnol-induced modulation of male reproductive function was explored. In this study, adult male rats were randomized into six groups of six rats each: the control received 1 ml of distilled water as vehicle, while the low- and high-dose Rohypnol-treated groups received 2 mg/kg and 4 mg/kg of Rohypnol for four weeks. The control-, low-, and high-dose recovery groups received 2 mg/kg and 4 mg/kg of Rohypnol for four weeks, respectively, which was followed by a 4-week drug-free recovery period. Rohypnol treatments led to impaired steroidogenesis and spermatogenesis and low sperm quality. This was accompanied by a rise in the markers of testicular injury, oxidative stress, inflammation, and apoptosis. Also, the activities of testicular enzymatic antioxidants and proton pumps were significantly reduced. Although the impacts of low-dose Rohypnol treatment were partially reversible, those of the high-dose Rohypnol treatment were not. Histopathological findings on the testicular tissues were in tandem with the biochemical alterations. Thus, it is safe to infer that Rohypnol induces testicular damage by the suppression of Na+/K+-ATPase and Ca2+-ATPase and the activation of caspase-3 through an oxidative-sensitive signaling pathway.

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“…Each measurement was taken by two experts who were blinded to the study protocol. The mean value obtained for each testis was used as the measurement for that testis [31,32].…”

Section: Assessment Of Testicularmentioning

confidence: 99%

“…Spermatogenic index, a pointer of spermatogenesis, was determined using the four-point system [21,32]. The number of the cell layers, cell types, and the presence of late spermatids in the seminiferous tubules were scored as follows:…”

Section: Assessment Of Testicularmentioning

confidence: 99%

Proton Pump Dysfunction and Upregulation of Caspase-3 Activity via Oxidative-Sensitive Signaling Mediate Rohypnol-Induced Testicular Toxicity

et al. 2023

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“…Methanolic M. oleifera leaf extract (MMOLE) was made as earlier reported (Sofowora, 1993;Ogundola et al, 2021). Fresh leaves of Moringa oleifera were air-dried for 2 weeks and pulverized using electric blender.…”

Section: Preparation Of Plant Extractmentioning

confidence: 99%

Methanolic Moringa oleifera leaf extract protects against epithelial barrier damage and enteric bacterial translocation in intestinal I/R: Possible role of caspase 3

Afolabi

Akhigbe

et al. 2022

Front. Pharmacol.

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Background: Activation of caspase 3 has been implicated in the pathogenesis of I/R injury in various organs, but there is a paucity of data on its role in IIRI. Also, no reports were found on the beneficial role of methanolic Moringa oleifera leaf extract (MMOLE) in IIRI. This study investigated the involvement of caspase 3 in IIRI, and the impact of MMOLE in IIRI.Methods: Male Wistar rats were randomized into five groups; the sham-operated group that was sham-operated and received 0.5 ml of distilled water for 7 days prior to sham surgery, and the IIRI, febuxostat (FEB) +IIRI, low dose MMOLE (LDMO)+IIRI, and high dose MMOLE (HDMO)+IIRI groups that underwent I/R and also received 0.5 ml of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of MMOLE, and 400 mg/kg of MMOLE respectively for 7 days prior to I/R. Markers of hepatic function, oxidative stress, and inflammation as well as enteric bacterial translocation and histoarchitecture integrity of intestinal and hepatic tissues were evaluated. The bioactive components of MMOLE were also determined by GC-MS.Results: As revealed by GC-MS, the active bioactive components of MMOLE were thiosemicarbazone, hydrazine, 1,3-dioxolane, octanoic acid, 1,3-benzenediamine, 9-octadecenoic acid, oleic acid, nonadecanoic acid, 3-undecanone, phosphonic acid, and cyclopentanecarboxylic acid. MMOLE alleviated IIRI-induced rise in intestinal and hepatic injury markers, malondialdehyde, TNF-α, IL-6, and myeloperoxidase activities. MMOLE improved IIRI-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase and glutathione peroxidase activities. These were associated with suppression of IIRI-induced caspase 3 activity and bacterial translocation. Histopathological evaluation revealed that MMOLE attenuated IIRI-induced alterations in intestinal and hepatic histoarchitecture integrity. MMOLE also militated against increased absolute and relative intestinal and hepatic weight, intestinal and hepatic injuries, epithelial mucosal barrier dysfunction, and enteric bacterial translocation associated with IIRI by downregulating oxidative stress-mediated activation of caspase 3.Conclusion: IIRI is associated with a rise in caspase 3 activity. Also, MMOLE confers protection against IIRI, possibly due to its constituent bioactive molecules, especially hydrazine, 9-octadecenoic acid, 1,3-dioxolane, oleic acid, and nonadecanoic acid.

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“…Preparation of plant extract has previously been reported [26,27]. The leaves of Phyllanthus amarus were air-dried for two weeks and pulverized using an electric blender.…”

Section: Preparation Of Plant Extractmentioning

confidence: 99%

Restoration of Hepatic and Intestinal Integrity by Phyllanthus amarus Is Dependent on Bax/Caspase 3 Modulation in Intestinal Ischemia-/Reperfusion-Induced Injury

et al. 2022

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Ethnopharmacological relevance: Oxidative stress is a key player in intestinal ischemia/reperfusion (I/R) injury (IIRI) with a tendency to trigger systemic inflammatory response, resulting in progressive distal organ injury. To date, the role of Bax/caspase 3 signaling in IIRI has not been reported. Furthermore, the discovery of a safe and effective drug remains pertinent in improving the outcome of IIRI. Therefore, this study investigated the role of Bax/caspase 3 signaling in intestinal I/R-induced intestinal and hepatic injury. In addition, the protective effect and possible associated mechanism of action of methanolic Phyllanthus amarus leaf extract (PA) against intestinal I/R-induced intestinal and hepatic injury were evaluated. Materials and methods: Fifty male Wistar rats were randomized into five groups (n = 10). The sham-operated group was received 0.5 mL of distilled water for seven days prior to the sham surgery, while the IIRI, febuxostat (FEB) + IIRI, low-dose PA (LDPA) + IIRI, and high-dose PA (HDPA) + IIRI groups underwent the I/R procedure. In addition to the procedure, IIRI, FEB + IIRI, LDPA + IIRI, and HDPA + IIRI received 0.5 mL of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of PA, and 400 mg/kg of PA, respectively, for seven days prior to the I/R procedure. Results: Administration of methanolic Phyllanthus amarus leaf extracts attenuated the intestinal I/R-induced rise in intestinal and hepatic injury markers, malondialdehyde, nitric oxide, TNF-α, IL-6, and myeloperoxidase activities. In addition, Phyllanthus amarus ameliorated I/R-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase, and glutathione peroxidase activities in intestinal and hepatic tissues. These were coupled with the suppression of I/R-induced bacterial translocation, downregulation of I/R-induced activation of Bax/caspase 3 signaling, and improvement of I/R-induced distortion of intestinal and hepatic histoarchitecture by Phyllanthus amarus. Conclusion: Methanolic Phyllanthus amarus leaf extract protects against intestinal and hepatic injuries associated with intestinal I/R by suppressing oxidative-stress-mediated activation of Bax/caspase 3 signaling. The beneficial effects of Phyllanthus amarus may be ascribed to its constituent bioactive molecules, especially tannins, anthocyanin, alkaloids, and phenolics.

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Contraceptive potential of Andrographis paniculata is via androgen suppression and not induction of oxidative stress in male Wistar rats

Cited by 13 publications

References 35 publications

Proton Pump Dysfunction and Upregulation of Caspase-3 Activity via Oxidative-Sensitive Signaling Mediate Rohypnol-Induced Testicular Toxicity

Proton Pump Dysfunction and Upregulation of Caspase-3 Activity via Oxidative-Sensitive Signaling Mediate Rohypnol-Induced Testicular Toxicity

Methanolic Moringa oleifera leaf extract protects against epithelial barrier damage and enteric bacterial translocation in intestinal I/R: Possible role of caspase 3

Restoration of Hepatic and Intestinal Integrity by Phyllanthus amarus Is Dependent on Bax/Caspase 3 Modulation in Intestinal Ischemia-/Reperfusion-Induced Injury

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