Morinda officinalis oligosaccharides mitigate depression-like behaviors in hypertension rats by regulating Mfn2-mediated mitophagy

Abstract

Objective Patients with hypertension have a risk of depression. Morinda officinalis oligosaccharides (MOOs) have anti-depressant properties. In this study, we aimed to determine whether MOOs can improve the symptoms of depression in individuals with hypertension. Methods Dahl salt-sensitive rats fed with a high-salt diet were stimulated by chronic unpredictable mild stress to mimic hypertension with depression. Primary astrocytes and neurons were isolated from these rats. Astrocytes underwent LPS stimulation to simulate the inflammatory astrocytes during depression. MOOs were administrated at 0.1 mg/g/day in vivo and 1.25, 2.5, and 5 mg/mL in vitro. Mitophagy was inhibited using 5 mM 3-methyladenine (3-MA). Astrocyte-mediated neurotoxicity was detected by co-culturing astrocytes and neurons. Results MOOs decreased systolic pressure, diastolic pressure, and mean arterial pressure, thereby improving depression-like behavior, including behavioral despair, lack of enthusiasm, and loss of pleasure during hypertension with depression. Furthermore, MOOs inhibited inflammation, astrocytic dysfunction, and mitochondrial damage in the brain. Then, MOOs promoted autophagosome and lysosome enriched in mitochondria in LPS-stimulated astrocytes. MOOs suppressed mitochondrial damage and the release of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in astrocytes undergoing LPS stimulation. Importantly, MOOs rescued the impaired neurons co-cultured with astrocytes. The effects of MOOs on LPS-stimulated astrocytes were reversed by 3-MA. Finally, MOOs upregulated LPS-downregulated Mfn2 expression in astrocytes. Mfn2 inhibition partly reversed the effects of MOOs on hypertension with depression. Intriguingly, Mfn2 suppression activated PI3K/Akt/mTOR pathway during MOOs treatment. Conclusions Astrocytes develop neuroinflammation in response to mitochondrial damage during hypertension with depression. MOOs upregulated Mfn2 expression to activate the PI3K/Akt/mTOR pathway-mediated mitophagy, thereby removing impaired mitochondria in astrocytes. Highlights MOOs have anti-hypertensive and anti-depressive properties. MOOs inhibit inflammation and injury in astrocytes during hypertension with depression. MOOs induce mitophagy activation in inflammatory astrocytes with mitochondrial damage. MOOs upregulate Mfn2 expression in astrocytes. Mfn2 activates mitophagy to resist mitochondrial damage in astrocytes.

Protective effects of Dioscin against sepsis‐induced cardiomyopathy via regulation of toll‐like receptor 4/MyD88/p65 signal pathway

“… 37 , 48 Former research indicated that diseases induced by LPS in rat models are linked to abnormalities in hemodynamic parameters. 49 , 50 It has been documented that after treatment with LPS in rats, the HR and HWI are augmented, while LVEF and MAP are lessened, 37 , 38 which was consistent with our findings. We also confirmed that Dioscin reversed the effects of LPS on HR, HWI, LVEF, and MAP in SIC rats.…”

“…LPS, a major component of the outer membrane of Gram‐negative bacteria, is frequently used to induce SIC in rats as an important immunomodulator 37,48 . Former research indicated that diseases induced by LPS in rat models are linked to abnormalities in hemodynamic parameters 49,50 . It has been documented that after treatment with LPS in rats, the HR and HWI are augmented, while LVEF and MAP are lessened, 37,38 which was consistent with our findings.…”

Rubiadin-1-methyl ether inhibits BECN1 transcription and Beclin1-dependent autophagy during osteoclastogenesis by inhibiting NF-κB p65 activation

“…Previous study showed that M. officinalis oligosaccharides can regulate mitochondrial autophagy in astrocytes. 21 Our results identified the inhibitory effect of another extract from M. officinalis How. on RANKL-induced OCP autophagy.…”

Chinese herbal medicines for the treatment of depression: a systematic review and network meta-analysis

“…Inflammation and mitochondrial dysfunction are also associated with the pathogenesis of depression ( Bansal and Kuhad, 2016 ; Kohler et al, 2016 ). In addition, Morinda Officinalis Oligosaccharide Capsule mitigate depression by regulating Mitofusin two protein-mediated mitophagy in rats ( Yang et al, 2023 ). Morinda Officinalis Oligosaccharide Capsule mainly contains inulin-type oligosaccharides extracted from the roots of M. officinalis, which is effective in ameliorating symptoms of depressive disorder ( Zhang et al, 2018 ).…”