Hydroxy-alpha-sanshool
Hydroxy-alpha-sanshool exerts antiobesity and hypolipidemic activities in HFD rats by reducing liver oxidative stress and thus could be considered as a potential candidate drug to cure or prevent obesity and hyperlipidemia. It also has analgesic properties, it activates TRPV1 and TRPA1 in sensory neurons.
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Biophysical Journal, 2012, 102(3):323a.
The Plant-Derived Alkylamide, Hydroxy-Alpha-Sanshool, Induces Analgesia through Inhibition of Voltage-Gated Sodium Channels[Reference:
WebLink]
Many native cultures use extracts from Xanthozylum plants to topically treat toothache and joint pain. One active component of these extracts is the alkylamide, Hydroxy-alpha-sanshool, which induces tingling and numbing paresthesia when applied to the skin or tongue. To understand the physiological mechanisms underlying paresthesias, we sought to identify the molecular targets of sanshool in the somatosensory system.
METHODS AND RESULTS:
We first measured the analgesic properties of sanshool using mouse models of somatosensory behavior. Topical application of sanshool on the hind paw of naïve mice did not alter their sensitivity to noxious thermal or mechanical stimuli. However, in a model of neurogenic inflammation, sanshool acutely suppressed inflammatory hypersensitivity to mechanical force whereas it did not suppress hypersensitivity to heat. These data suggest that sanshool inhibits activity of a subset of sensory neurons that transduce mechanical, but not thermal, stimuli. In cultured dorsal root ganglion (DRG) neurons from mice, sanshool inhibited action potential (AP) firing in a subset of medium-to-large diameter neurons, which are thought to mediate mechanotransduction. In contrast, sanshool did not inhibit AP firing in small-diameter sensory neurons, which predominantly transduce noxious heat. In addition to size, sensory neurons are distinct in their expression of sensory neuron-specific voltage-gated sodium channels. Thus the differential effect of sanshool on sensory neurons may be due to selective activity of sanshool on different sodium channels. To test this idea, we compared the effects of sanshool on two sodium channel subtypes that are expressed in sensory neurons, Nav1.7 and 1.8.
Sanshool reduced the magnitude of Nav1.7 and Nav1.8 currents but caused a hyperpolarizing shift in the steady-state inactivation curve of Nav1.7 only.
CONCLUSIONS:
Thus intrinsic molecular differences between sensory neurons, such as expression of different sodium channel subtypes, may underlie specificity of sanshool action.
Oxid Med Cell Longev. 2019 Aug 27;2019:5852494.
Antiobesity, Regulation of Lipid Metabolism, and Attenuation of Liver Oxidative Stress Effects of Hydroxy-α-sanshool Isolated from Zanthoxylum bungeanum on High-Fat Diet-Induced Hyperlipidemic Rats.[Pubmed:
31534622 ]
Zanthoxylum bungeanum is a traditional Chinese medicine (TCM) used to relieve pain, dispel dampness, stop diarrhea, and prevent itching. The aim of this study was to investigate the antiobesity and hypolipidemic effects of Hydroxy-alpha-sanshool (HAS) isolated from Z. bungeanum on hyperlipidemic rats.
METHODS AND RESULTS:
Wistar rats (n = 48) were randomly divided into six groups: (1) normal diet rats (ND), (2) high-fat diet- (HFD-) treated rats, (3) HFD+fenofibrate-treated rats (HFD+FNB), (4) HFD+low dose of HAS-treated rats (HFD+LD, 9 mg/kg), (5) HFD+middle dose of HAS-treated rats (HFD+MD, 18 mg/kg), and (6) HFD+high dose of HAS-treated rats (HFD+HD, 36 mg/kg). The body weight and food intake of the rats were recorded during the treatment period. After 4 weeks of HAS treatment, abdominal adipose tissues were observed and total cholesterol (T-CHO), triglycerides (TG), high-density lipoprotein (HDL) cholesterol (HDL-C), and low-density lipoprotein (LDL) cholesterol (LDL-C) of serum and liver tissues were determined. Furthermore, histochemical examinations using oil red O and hematoxylin-eosin staining (H&E) were carried out and levels of malondialdehyde (MDA) and glutathione (GSH) and activities of superoxide dismutase (SOD) in the liver were determined. After HFD feeding, the body weight gain and food efficiency ratio of HFD rats were significantly enhanced (p < 0.05vs. ND rats) and HAS treatment (18 and 36 mg/kg) significantly decreased the body weight gain and food efficiency ratio (p < 0.05vs. HFD rats). In addition, HAS treatment could decrease the abdominal adipose tissues and liver adipocytes. Furthermore, HAS treatment significantly decreased the T-CHO, TG, and LDL-C, whereas it increased HDL-C (p < 0.05vs. HFD rats) in serum and the liver. HAS treatment increased the GSH level and SOD activity in the liver (p < 0.05vs. HFD rats), whereas it decreased the levels of MDA (p < 0.05vs. HFD rats). mRNA analyses suggested that HAS treatment increases the expression of Pparg (proliferator-activated receptor γ) and Apoe (peroxisome apolipoprotein E). Immunohistochemistry and Western blotting indicated that HAS stimulation increased the levels of PPARγ and APOE in the liver, as a stress response of the body defense system.
CONCLUSIONS:
These results revealed that HAS exerts antiobesity and hypolipidemic activities in HFD rats by reducing liver oxidative stress and thus could be considered as a potential candidate drug to cure or prevent obesity and hyperlipidemia.
