Abstract
Dammarane steroids (DS) are a class of chemical compounds present in Panax ginseng. Here, we evaluated the effect of 10 weeks of DS supplementation on inflammatory modulation in the soleus muscle following eccentric exercise (EE)-induced muscle damage (downhill running). Eighty rats were randomized into 4 groups of DS supplementation (saline, 20, 60, 120 mg/kg body weight). Inflammatory markers were measured at rest and again 1 h after EE. At rest, NFκB signaling, TNF-alpha and IL-6 mRNAs, 3-nitrotyrosine, glutathione peroxidase, and GCS (glutamylcysteine synthetase) levels were significantly elevated in the skeletal muscle of DS-treated rats in a dose-dependent manner. Additionally, there were no detectable increases in the number of necrotic muscle fibers or CD68+ M1 macrophages. However, muscle strength, centronucleation, IL-10 mRNA expression, and the number of CD163+ M2 macrophages increased significantly over controls with DS treatment in rat soleus muscle. Under EE-challenged conditions, significant increases in muscle fiber necrosis, CD68+ M1 macrophage distribution, and 3-nitrotyrosine were absent in rats that received low and medium doses (20 and 60 mg/kg) of DS treatment, suggesting that DS possess anti-inflammatory action protecting against a muscle-damaging challenge. However, this protective activity was diminished when a high dose of DS (120 mg/kg) was administered, suggesting that DS possess hormetic properties. In conclusion, our study provides new evidence suggesting that DS is an ergogenic component of ginseng that potentiate inflammation at baseline but that produce anti-inflammatory effects on skeletal muscle following muscle-damaging exercise. Furthermore, high doses should be avoided in formulating ginseng-based products.
Highlights
Inflammation, an innate immune response, plays a key role in eliminating unhealthy cells generated by various adverse conditions [1]; this process is essential for the regeneration of new muscle fibers after damage [2]
In non-exercised rats, there was no increase in necrotic muscle fibers (Fig. 2A) or CD68+ M1 macrophages (Fig. 2B) in skeletal muscle with Dammarane steroids (DS) treatment
The major findings of the study are (1) the ginseng-derived steroids DS can potentiate inflammatory signaling of skeletal muscle in a dose-dependent manner, as evidenced by increases in nitrotyrosine levels, NFkB signaling, and gene expression of pro-inflammatory mediators, without apparent muscle fiber injury or CD68+ M1 macrophage invasion in skeletal muscle; (2) muscle strength can be increased by long-term DS supplementation at all doses tested; and (3) muscle damage, nitrotyrosine levels, and CD68+ M1 macrophage infiltration induced by EE can be minimized at low and medium DS doses, but this protective effect is diminished at a maximal dose
Summary
Inflammation, an innate immune response, plays a key role in eliminating unhealthy cells generated by various adverse conditions [1]; this process is essential for the regeneration of new muscle fibers after damage [2]. NFkB activation in damaged skeletal muscle facilitates an inflammatory response, which increases interleukin-1beta (IL-1b), tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) [3]. This response facilitates further clearance of damaged fibers by communicating with surrounding mononuclear cells. M1 macrophages are recruited to damaged muscle fibers, and free radicals are released to lyse cells in inflamed tissue [4]. Release of interleukin-10 (IL-10) from M2 macrophages is associated with inhibition of M1 macrophages to end the first destructive phase [4, 6]
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