99% Purity Osthole CAS 484-12-8 White Powder Treatment Of Male Sexual Dysfunction

1. Introduction

Osthole (also known as osthol), 7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one, is a natural coumarin first derived from Cnidium plant (Figure 1). High content of osthole is found in the mature fruit of Cnidium monnieri (Fructus Cnidii), which is commonly applied in clinical practice of Traditional Chinese Medicine (TCM) (Figure 2), while it is also widely found in other medicinal plants including Angelica, Archangelica, Citrus, Clausena. Fructus Cnidii strengthens immune system and improves male function, relieving rheumatic pain and eliminating dampness; most of these medicinal properties are considered to attribute to one of its major bioactive components, osthole [1, 2]. Modern researches have suggested that osthole exhibits antioxidant, anticancer, anti-inflammatory, and immunomodulatory properties [1, 3, 4]. With multiple bioactivities of osthole reported, developing osthole and derivatives as potential multitarget drug should be encouraged. Therefore, it is meaningful to summarize the pharmacological and biological researches on this coumarin, to review the mechanisms behind the effects and get a comprehensive picture of its miscellaneous functions.

2. Biological and Pharmacological Activities of Osthole

2.1. Nootropic and Neuroprotective Effect

The benefits of osthole and Fructus Cnidii (FC) extract on nervous system have been investigated in recent years. Osthole regulates ion channels and G protein-coupled receptor (GPCR) activities influencing neuronal and neuroendocrine function. Evidence suggested that osthole blocked L-type Ca2+ channel and Na+ channels in mouse neuronal cells . Osthole increased the affinity of thyrotropin-releasing hormone (TRH) receptor (one of GPCR), hence decreasing the binding of TRH to its receptor and suppressing TRH-evoked production of triphosphoinositol (IP3) and mobilization of sequestered Ca2+ in rat pituitary GH4C1 cells . In addition, Wang et al. examined the effect of osthole and imperatorin (another coumarin isolated from FC) on glutamate release from rat hippocampal synaptosomes. The results suggested that both chemicals facilitated 4-aminopyridine- (4-AP-) evoked glutamate release by activating N-and P/Q-type Ca2+ channel through a signaling cascade involving protein kinase C (PKC) . Lin et al. then suggested osthole-facilitated glutamate release was related to increased synaptic vesicle availability for exocytosis  and to activation of cGMP/PKG-dependent pathway . Osthole was also found to reduce acid-sensing ion channel 3 (ASIC3) expression in rat dorsal root ganglion, which may contribute to its relieving chronic pain from lumbar disc herniation. Moreover, Luszczki et al. reported that osthole showed anticonvulsant effect in maximal electroshock seizure models, suggesting its potential in seizure treatment . Osthole was identified as a modulator of the neurotransmitter gamma-aminobutyric acid (GABA)A receptor in vitro, which provided a possible mechanism explaining such antiseizure effect .

On the other hand, osthole exhibited neuroprotective effects against neurodegeneration in both in vitro and in vivo experimental models. Pretreatment of osthole showed significant protective effect on viability of PC12 cells exposed to neurotoxin MPP+, an in vitro model of Parkinson’s disease . Moreover, multiple evidences have demonstrated the protective effect of osthole on alleviating brain damage and improving neurobehavioral functions caused by both chronic  and acute  ischemia due to its antioxidative and anti-inflammatory properties, through mitogen-activated protein kinase (MAPK) pathway by prolonged activation of ERK1/2 and suppression of JNK activity . Osthole has also been suggested as a promising herbal component for memory loss therapy . Animal experiments have been conducted in aluminium chloride- (AlCl3-) induced acute senile model  and scopolamine-induced amnesia model , and results from both studies demonstrated ameliorating effect on memory impairment. In addition, studies demonstrated that osthole was also effective in treating traumatic brain injury by significantly reducing neurological deficits, cerebral edema, and hippocampal neuron loss , as well as relieving spatial performance deficits in scopolamine- (SCOP-) treated or ovariectomized (OVX) rats  and attenuating autoimmune encephalomyelitis in mice