# Current Progress Regarding _Cordyceps militaris_, Its Metabolite Function, and Its Production
## 2 Biological Compounds of _C. militaris_
### Lowastatin  
Lovastatin, found in the fruiting bodies of _C. militaris_[17; 120], is a type of statin that selectively blocks the synthesis of endogenous cholesterol by inhibiting the rate-limiting enzyme in cholesterol production. Lovastatin features a six-membered lactone ring alongside a hydroxyl group and a partially hydrogenated naphthalene, with a hydroxyl substituent esterified by a 2-methylbutyric acid residue. Its molecular formula is C\({}_{24}\)H\({}_{36}\)O\({}_{5}\), with a molecular weight of 404.54 g/mol. It is converted from a lactone to a hydroxy acid form during enzymatic reactions, and this form competitively blocks 3-hydroxymethylylglutaryl-coenzyme A (HMG-CoA) [121]. The lovastatin concentration in the mycelium of _C. militaris_ ranged from 37.7-57.3 mg/kg DW, which was lower than the concentration found in _C. sinensis_ at 1365.3 mg/kg [17]. Fruiting bodies of _C. militaris_ contain lovastatin at a concentration of 2.76 mg/kg. However, the fruiting bodies of _Hercium erinaceous_ and _Ganoderma lucidum_ exhibit some of the highest lovastatin contents, at 14.38 and 11.54 mg/kg, respectively [16]. Approved for treating hypercholesterolemia and reducing the risk of coronary heart disease, lovastatin also exhibits additional beneficial effects such as anti-inflammatory and antioxidant properties, as well as vascular endothelium protection [122].  
Upon oral administration, lovastatin was found to reduce oxidative stress and modulate activities of antioxidant enzymes in the liver and heart tissues of H\({}_{2}\)O\({}_{2}\)-treated rats, indicating its potential in mitigating the effects of oxidative stress [65].  
Lovastatin inhibits the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling pathway and downregulates histone deacetylase 1 (HDAC1) expression, which prevents cytosolic NF-kB from entering the nuclei of LPS-stimulated RAW264.7 macrophages. Additionally, it reduces expressions of iNOS and TNF-\(\alpha\) and induces an anti-inflammatory response [67].  
By directly inhibiting hydroxymethylglutaryl coenzyme A reductase, lovastatin inhibits the prenylation pathways in cells. It was found to reduce respiratory syncytial virus (RSV) replication when administered within 24 h after infection, but not vaccinia virus replication. In mice, lovastatin also decreases virus-induced weight loss and illness, indicating its potential as a therapeutic agent for RSV infection [123].  
Lovastatin was demonstrated to enhance the antitumor effects of cisplatin and TNF-\(\alpha\), as well as to increase apoptosis induced by cisplatin, 5-fluorouracilacil, and sulindac in colon cancer cells [124].  
Lovastatin plays an important role in inducing the expression of thrombomodulin, a gene with antithrombotic properties. Moreover, it decreases the expressions of prothrombotic factors such as E-selectin, plasminogen activator inhibitor type 1 (PAI-1), vascular cell adhesion molecule (VCAM)-1, intracellular cell adhesion molecule (ICAM)-1, and endothelin [125] and enhances the expression of the endothelial (_e_)_NOS_ gene. Studies suggested that endothelial _NOS_ expression is closely linked to thrombomodulin expression [126].  
Lovastatin is effective as an antiatherosclerotic drug and a cell-cycle blocker due to its ability to induce cell-cycle arrest or retardation in various cell types. This effect is not only limited to the G\({}_{1}\) phase but also affects the G\({}_{2}\)/M transition. Upon incubation of epithelial PtK2, T24, HeLa, and fibrobl L929 cells with 1.0-60.0 um lovastatin for 24-48 h, various mitotic perturbations were observed [127].