The Extract of Arctium lappa L. Fruit (Arctii Fructus) Improves Cancer-Induced Cachexia by Inhibiting Weight Loss of Skeletal Muscle and Adipose Tissue

Abstract

Background: Cachexia induced by cancer is a systemic wasting syndrome and it accompanies continuous body weight loss with the exhaustion of skeletal muscle and adipose tissue. Cancer cachexia is not only a problem in itself, but it also reduces the effectiveness of treatments and deteriorates quality of life. However, effective treatments have not been found yet. Although Arctii Fructus (AF) has been studied about several pharmacological effects, there were no reports on its use in cancer cachexia. Methods: To induce cancer cachexia in mice, we inoculated CT-26 cells to BALB/c mice through subcutaneous injection and intraperitoneal injection. To mimic cancer cachexia in vitro, we used conditioned media (CM), which was CT-26 colon cancer cells cultured medium. Results: In in vivo experiments, AF suppressed expression of interleukin (IL)-6 and atrophy of skeletal muscle and adipose tissue. As a result, the administration of AF decreased mortality by preventing weight loss. In adipose tissue, AF decreased expression of uncoupling protein 1 (UCP1) by restoring AMP-activated protein kinase (AMPK) activation. In in vitro model, CM increased muscle degradation factors and decreased adipocytes differentiation factors. However, these tendencies were ameliorated by AF treatment in C2C12 myoblasts and 3T3-L1 cells. Conclusion: Taken together, our study demonstrated that AF could be a therapeutic supplement for patients suffering from cancer cachexia.

Reducing White Adipose Tissue Browning Using p38α MAPK Inhibitors Ameliorates Cancer-Associated Cachexia as Assessed by Magnetic Resonance Imaging

“…However, further investigation from this work suggests that the p38α-specific inhibitor VCP979 has a more prominent effect on inhibiting adipocyte differentiation and ameliorating CAC. Importantly, our results are consistent with those reported by Felipe Henriques et al [ 52 ] and Han et al [ 53 ], all supporting that the suppression of adipose tissue browning induced by CAC can increase survival and p38α could serve as a novel druggable target to combat metabolic diseases such as cachexia.…”

Diagnostic Ability of Methods Depicting Distress of Tumor-Bearing Mice

“…In our study, this readout parameter was uninformative for differentiating between baseline data and data derived from tumor-bearing mice. This is inconsistent with the widely published concept that severe weight loss can be observed in some animal models during tumor growth [ 20 , 33 ]. However, several other publications also describe that the total body weight was not reduced in tumor-bearing mice [ 34 , 35 , 36 , 37 , 38 ].…”

“…Some authors also mention that the weight of the tumor itself and intraperitoneal effusion may mask the body weight loss [ 39 ]. Another study on a mouse xenograft model demonstrated that the size of subcutaneous tumors increased the total body weight of tumor-bearing mice [ 33 ]. However, these studies did not compare the adjusted body weight to other readout parameters for distress and did not address the issue if adjusted body weight change has the diagnostic ability to differentiate between mice with and without a tumor.…”

Phytochemicals and Biological Activities of Burdock (Arctium lappa L.) Extracts: A Review

“…Furthermore, polysaccharides obtained from extracts of A. lappa regulated lipid metabolism in animal models for type 1 and 2 diabetes [79,80] . Different other properties have also been reported as effective in the treatment of several conditions including, acne, [130] anti‐aging, [44,131] antiobesity, [89] skin whitening agent, [19] anti‐constipation and intestinal flora regulation, [83] neuroprotective effect, [13,82] hepatoprotective, [7,78,86] anti‐tuberculosis, [61] anti‐ulcer, [24,56] and cachexia induced by cancer [132] …”