n -Butanol Fraction of Ligustrum lucidum Benefits Muscular Function and Myofibers of Aging Ovariectomized Mice and Rats by Retarding Senescence-Related Events in Skeletal Muscle

Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum, is used in traditional Chinese medicine to treat aging-related symptoms. This study aimed to explore the regulatory effects of the n-butanol phenol glycosides-enriched fraction of FLL on muscular function and senescence-relevant biological events, such as fibrosis, senescence-associated secretory phenotypes (SASPs), activity of the renin-angiotensin system (RAS), and insulin resistance, in skeletal muscle. Naturally aging rats and D-gal-induced aging mice, both of which underwent bilateral ovariectomy, were orally administered with the n-butanol fraction of FLL for 8 weeks by intragastric gavage. Muscular functions were determined by the grip strength test and weight-loaded swimming test. The frozen sections of muscle tissue were subjected to several types of staining, and senescence-associated hallmarks, (pro)fibrotic factors, RAS components, and insulin signaling were detected in the serum and muscle by ELISA, PCR, and immunoblotting. The FLL fraction elevated muscle mass, improved muscle strength, and augmented the cross-sectional area of gastrocnemius fibers. It furthermore reversed changes in the expression of myogenic regulatory factors, inhibited the SASP and protein expression of senescent hallmarks, repressed the over-activity of muscular RAS (renin/Ang II), and reduced the fibrotic area and expression of type I and III collagens in the gastrocnemius. Moreover, abnormal alterations in protein expression (IRß/IRS-1/AKT/GSK-3ß signaling) were improved in the muscle. The in vivo study of 20-month-old ovariectomized rats confirmed the benefits of this fraction on muscle mass and myofiber area, as well as its inhibitory effects on both the accumulation of SA-ß-gal and collagen molecules and enhanced muscle myostatin levels and RAS activity. In addition, it promoted the distribution percentage of type IIb myofibers in the tibialis anterior muscle. Collectively, the n-butanol phenol glycosides-enriched fraction of FLL could be a potential source for novel and/or lead drugs for the treatment of muscle atrophy and sarcopenia in elderly women.