Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling

Abstract

BackgroundCachexia has a devastating impact on survival and quality of life for many cancer patients and contributes to nearly one‐third of all cancer deaths; also, it is associated with poor responses to chemotherapy and survival. A better understanding of the underlying mechanisms of cancer‐associated cachexia (CAC), coupled with effective therapeutic approaches, will improve management of progressive functional impairment in cancer patients. Salidroside, a phenylpropanoid glycoside in Rhodiola rosea L, has been reported to possess potential anti‐fatigue, anti‐ageing, and anti‐Alzheimer's disease properties. It is widely consumed as a nutritional supplement, but its effects on CAC and the possible mechanism remain a mystery.MethodsIn the murine models of cachexia induced by CT‐26 and Lewis lung carcinoma (LLC) tumour, respectively, main features of CAC were determined after treatment of salidroside or chemotherapy. In vitro experiments were performed using murine C2C12 myotubes, which were treated by tumour necrosis factor‐α. Levels of several critical muscle‐related signal proteins such as mammalian target of rapamycin (mTOR), p‐mTOR, and myosin heavy chain (MyHC) were examined using western blot both in vitro and in vivo.ResultsIn the present study, we showed the exciting effect of salidroside on the treatment of CAC. In CT‐26 and LLC models, respectively, salidroside treatment could effectively preserve the tumour‐free body weight, decrease loss of adipose and gastrocnemius muscles, alleviate tumour burden, and prolong their survival time. Additionally, in combined chemotherapy, salidroside could synergistically enhance the anti‐tumour activity of cisplatin, especially decreased or eliminated chemotherapy‐induced cachexia. Further analysis demonstrated that salidroside could significantly increase expression of mTOR, p‐mTOR, and MyHC in gastrocnemius muscle. Also, results in vitro showed that salidroside could not only obviously increase mTOR, p‐mTOR, and MyHC expression in C2C12 myotubes but also effectively rescue their down‐regulation induced by tumour necrosis factor‐α.ConclusionsIn the current study, the exciting effect of salidroside on CAC suggested that salidroside supplementation might be a promising approach for a multi‐targeted therapy for the treatment of CAC.

Rhodiola rosea L.: an Herb with Anti-Stress, Anti-Aging, and Immunostimulating Properties for Cancer Chemoprevention

“…In addition, salidroside was shown to promote angiogenic differentiation of human bone marrow-derived endothelial progenitor cells [105] and to protect against oxidative endothelial injury by activation of the mTOR pathway [105–107]. Salidroside also inhibited CT-26 and Lewis lung carcinoma tumor-induced cachexia and the loss of tumor-free body weight, adipose and gastrocnemius muscles, as well as extended the survival of the treated mice by increasing the expression of phosphorylated mTOR both in C2C12 myotubes and in gastrocnemius muscle of the mice [108]. These results suggested that salidroside has a text-dependent effect on the mTOR pathway.…”

Preventing muscle wasting by osteoporosis drug alendronate in vitro and in myopathy models via sirtuin‐3 down‐regulation

“…have also indicated that dihydrotestosterone could rescue an age‐dependent reduction in protein synthesis of skeletal muscle fibres in sarcopenic mice . A natural product, salidroside, sourced from Rhodiola rosea L., has been found to exhibit potential therapy against cancer‐associated cachexia‐induced limb muscle loss in tumour‐borne BALB/c mice, including gastrocnemius (Gascn) muscles . Moreover, anamorelin, a ghrelin‐analog, could show an increase in muscle mass in cancer anorexia‐cachexia syndrome .…”

“…20 A natural product, salidroside, sourced from Rhodiola rosea L., has been found to exhibit potential therapy against cancer-associated cachexia-induced limb muscle loss in tumour-borne BALB/c mice, including gastrocnemius (Gascn) muscles. 21 Moreover, anamorelin, a ghrelin-analog, could show an increase in muscle mass in cancer anorexia-cachexia syndrome. 22 It is critical to discover the potential interventions against muscle wasting from sarcopenia, cachexia, and other diseases.…”

Contemporary publication patterns in the Journal of Cachexia, Sarcopenia and Muscle by type and sub‐speciality: facts and numbers

“…The future pipeline of therapeutic interventions will be enhanced by the dissemination of basic reports into preclinical models [34][35][36][37] and early human trials 38 as a way of evaluating novel interventions. [39][40][41][42] One of the major advantages of having JCSM as a leader in this field is that such opportunities can more easily be found, rather than being spread over dozens of different journals.…”

“…27,28 There was growing evidence for the development of clinical trials and for improvements in clinical trial methodology by the development and validation of clinical screening tools 29 and scoring systems, 30 biomarkers, 31,32 and evaluative methodologies, including the establishment of normal ranges. 33 These may help make trial design and novel treatment evaluation more precise in the future.The future pipeline of therapeutic interventions will be enhanced by the dissemination of basic reports into preclinical models [34][35][36][37] and early human trials 38 as a way of evaluating novel interventions. [39][40][41][42] One of the major advantages of having JCSM as a leader in this field is that such opportunities can more easily be found, rather than being spread over dozens of different journals.There was a noticeable increase compared to earlier years of the journal in orthopaedic and musculoskeletal clinical reports.…”