The ameliorative effect of monotropein, astragalin, and spiraeoside on oxidative stress, endoplasmic reticulum stress, and mitochondrial signaling pathway in varicocelized rats

Abstract

Background: Monotropein, astragalin, and spiraeoside (MAS) are active compounds extracted from medicinal herbs; monotropein from Morinda officinalis How (Rubiaceae), astragalin (kaempferol 3-O-glucoside) from Cuscuta chinensis Lamark (Convolvulaceae) and spiraeoside from the outer scales of Allium cepa L. (Liliceae) in a ratio of 6.69:0.41:3.61. Monotropein, astragalin, and spiraeoside are well-known antioxidants, anti-inflammatory, and antinociceptive agents. The current investigation aims to study the molecular mechanism of varicocele-induced male infertility and the underlying pharmacological mechanisms of MAS. Methods: Four groups were included: control (CTR), MAS 200 group (MAS 200 mg/kg), varicocele group (VC), and VC + MAS 200 group (MAS 200 mg/kg). Sprague-Dawley (SD) rats were treated with 200 mg/kg MAS or vehicle once daily for 28 days. The possible signaling mechanism and effects of MAS were measured via histological staining, immunohistochemistry, western blot, and biochemical assays. Results: Parameters such as sperm motility and count, Johnsen's scores, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and expression of the steroidogenic acute regulatory protein (StAR) improved significantly in the VC + MAS 200 group compared with the VC group. MAS treatment of varicocele-induced group significantly decreased the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as testicular interleukin-6 (IL6), tumor necrosis factor-α (TNF-α), ROS/RNS, and malondialdehyde (MDA). It also decreased the apoptotic index and reduced the expression of endoplasmic reticulum (ER) protein levels (Grp78, p-IRE1α, and p-JNK) and apoptotic markers such as cleaved caspase-3 and Bax/Bcl2 ratio. Conclusion: This study suggests that the crosstalk between oxidative stress, ER stress, and mitochondrial pathway mediates varicocele-induced testicular germ cell apoptosis. MAS promotes spermatogenesis in varicocele-induced SD rat, probably by decreasing cytokines (IL-6, TNF-α) levels, regulating abnormal sex hormones, and decreasing oxidative stress, ER stress, and apoptosis.

Monotropein alleviates H2O2‑induced inflammation, oxidative stress and apoptosis via NF‑κB/AP‑1 signaling

“…Previous studies have demonstrated that Mtp exerts antiapoptotic and anti-inflammatory effects in osteoarthritis chondrocytes (21,24,25). nevertheless, the potential functions of Mtp in the progression of cVd are not completely understood.…”

MOTILIPERM Ameliorates Immobilization Stress-Induced Testicular Dysfunction via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway in SD Rats

“…Stress-induced testicular dysfunction and corresponding pathological features have been well documented in rats [26]. MOTILIPERM has been used as an antioxidant to reduce lipid peroxidation, scavenge free radicles, and prevent germ cell apoptosis in varicoceles and drug-induced testicular toxicity [19,20,[23][24][25]. The present study reported for the first time the effect of MOTILIPERM on reproductive parameters in immobilization stress-induced male infertility in adult SD rats.…”

“…The components of MOTILIPERM, Morinda officinalis How (Rubiaceae) root, Cuscuta chinensis Lamark (Convolvulaceae) seed, and Allium cepa L. (Liliaceae) outer scales, reportedly possess a wide spectrum of pharmacological activities, such as antioxidant, antinociceptive, and anti-inflammatory activities [8,17,18]. Due to the synergistic effects of polyherbal formulations, MOTILIPERM has a vast advantage over single herbal formulations [19,20]. The marker compounds in MOTILIPERM include monotropein, diacetyl asperulosidic acid, kaempferol 3-O-glucoside, quercetin 4 -O-glucoside, and quercetin [19,20].…”

“…Due to the synergistic effects of polyherbal formulations, MOTILIPERM has a vast advantage over single herbal formulations [19,20]. The marker compounds in MOTILIPERM include monotropein, diacetyl asperulosidic acid, kaempferol 3-O-glucoside, quercetin 4 -O-glucoside, and quercetin [19,20]. Monotropein and diacetyl asperulosidic acid is a major iridoid glycoside compound from Morinda officinalis How (Rubiaceae) root and exhibit actinociceptive, anticlastogenic, and anti-inflammatory activity [21].…”

“…Administration of MOTILIPERM can increase germ cell proliferation by protecting the testis from oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial-mediated apoptosis [19,23,24]. Furthermore, treatment with MOTILIPERM in varicocele-induced rat models restores testicular dysfunction by decreasing oxidative stress, ER stress, and germ cell apoptosis and upregulating testosterone synthesis [19,20]. However, the protective effect of MOTILIPERM against stress by immobilization-induced impairment of spermatogenesis and the possible molecular mechanisms thereof have never been documented.…”