An Evidence-Based Review of Medicinal Plants in the Overall Management of Chronic Fatigue

Background: Fatigue is generally a normal response to physical exertion or any stressful situation. Its prevalence rates have reached the level of 1.5-3% among the general population. Due to the unclear etiology, diagnostic ambiguity, and resultant heterogeneousness among the population, there is a lack of a solid treatment regimen for fatigue. As the absolute treatment option is vague, patients are moving towards complementary and alternative medicines. Hence it is mandatory to review the efficiency of complementary and alternative therapies along with herbal medicines. Objective: The purpose of this review is to carry out an evidence-based exploration of the potentiality of medicinal plants in the treatment and management of fatigue. Methods: This research was performed by conducting a literature review of the available studies from the PubMed database. Results: The study was based on 23 pre-clinical and clinical studies. It showed that medicinal herbs including Andrographis paniculata, Angelina sinensis, Astralagus membranaceus, Cordyceps sinensis, Panax ginseng, Gymnostemma pentaphyllum, Holy Basil, Lepidium meyenii, Rhodiola rosea, and Withania somnifera that belong to various traditional medicinal systems such as Ayurveda and Chinese Traditional Medicines can be a promising strategy to manage the various forms of fatigue. Conclusion: On the basis of these studies, it was concluded that the medicinal herbs and the phytochemicals within have a possible role in improving the symptoms associated with fatigue which can be further validated to produce targeted therapy for fatigue.

Cordycepin Attenuates Palmitic Acid-Induced Inflammation and Apoptosis of Vascular Endothelial Cells through Mediating PI3K/Akt/eNOS Signaling Pathway

A well-known medicinal mushroom in the field of traditional Chinese medicine, Cordyceps sinensis, is a rare natural-occurring entomopathogenic fungus, and it typically grows at high altitudes on the plateau of the Himalayan. Previous studies indicated that cordycepin, the main bioactive chemical of Cordyceps sinensis, has very potent anticancer, anti-oxidant and anti-inflammatory activities. However, its protective effects against atherosclerotic changes in vascular endothelial cells have not been fully elucidated. In this study, we showed that pretreatment with cordycepin significantly attenuated palmitic acid (PA)-induced cytotoxicity, reactive oxygen species (ROS) generation, and inflammatory responses. We found that PA decreased phosphorylation of Akt, eNOS, and bioavailability of nitric oxide (NO), which in turn activated NF-[Formula: see text]B and the downstream inflammatory responses. All these detrimental events were markedly blocked by pretreatment with cordycepin. Moreover, cordycepin ameliorated destabilization of mitochondrial permeability, cytosolic calcium rises, and apoptotic features caused by PA. In addition, all these anti-inflammatory and anti-apoptosis effects of cordycepin were found to be inhibited by the PI3K and eNOS inhibitor, suggesting that its anti-atherosclerotic effects may partially be mediated by the PI3K/Akt/eNOS signaling pathway.

Anti-oxidant and Anti-inflammatory Effects of Cordyceps militaris Extracts

This study investigated antioxidant and anti-inflammatory in order to confirm the possibility of functional materials that can improve skin diseases using <i>Cordyceps militaris</i> extracts. As a result of measuring the total polyphenol content in the solvent extract of Cordyceps sinensis extracted while decreasing the ethanol content, the content was high in 100% water, 30% ethanol, and 50% ethanol extract. As a result of measuring DPPH and ABTS free radical scavenging activities, it was confirmed that 100% water, 30% ethanol, and 50% ethanol extracts had superior antioxidant activity compared to other solvent extracts. In particular, in the case of 50% ethanol extract, it was confirmed that the antioxidant ability was excellent even at a low concentration compared to other extracts. As a result of confirming the efficacy of reducing skin inflammation against 50% ethanol extract using the HaCaT cell line, it was confirmed that the protein level of the CCL17 and CCL22 cytokine increased by TNF-αTNF-α/IFN-γ decreased by 77.8-81.5% and 61.9-67.4%, respectively. In conclusion, the 50% ethanol extract of <i>Cordyceps militaris</i> is likely to be used as a functional material related to skin diseases in the future.

Supercritical Carbon Dioxide Extracts of Cordyceps sinensis: Chromatography-based Metabolite Profiling and Protective Efficacy Against Hypobaric Hypoxia

The toxicity and disposal concerns of organic solvents used in conventional extraction purposes has entailed the need for greener alternatives. Among such techniques, supercritical fluid extraction (SFE) has gained popularity by yielding extracts of high purity in a much faster manner. Carbon dioxide (CO2) is generally preferred as a supercritical solvent because of its lower temperature requirements, better diffusivity and easy removal. The present study describes the characterization of supercritical CO2 extracts of Indian variety of Cordyceps sinensis (CS)- a high-altitude medicinal mushroom widely revered in traditional medicine for its extensive anti-hypercholesterolemic, anti-inflammatory, anti-proliferative and energy-enhancing properties. Experimental parameters viz. 300 and 350 bar of extraction pressure, 60°C of temperature, 0.4°L/h CO2 of flow rate and use of 1% (v/v) of ethanol as entrainer were optimized to prepare three different extracts namely, CSF1, CSF2 and CSF3. High-performance thin-layer chromatography (HPTLC) was used for assessing the quality of all the extracts in terms of cordycepin, the pivot biomarker compound in CS. Characterization by HPTLC and GC-MS confirmed the presence of flavonoids and nucleobases and, volatile organic compounds (VOCs), respectively. The chromatographic data acquired from metabolite profiling were subjected to chemometric analysis in an open source R studio which illustrated interrelatedness between CSF1 and CSF2 in terms of two major principal components. i.e. Dim 1 and Dim 2 whose values were 40.33 and 30.52% in variables factor map plotted using the HPTLC-generated retardation factor values. The factor maps based on retention times of the VOCs exhibited a variance of Dim 1 = 43.95% and Dim 2 = 24.85%. Furthermore, the extracts demonstrated appreciable antibacterial activity against Escherichia coli and Salmonella typhi by generation of reactive oxygen species (ROS), protein leakage and efflux pump inhibition within bacterial pathogens. CSFs were elucidated to be significantly cytoprotective (p &lt; 0.05) in a simulated hypobaric hypoxia milieu (0.5% oxygen). CSF2 showed the best results by effectively improving the viability of human embryonic kidney (HEK 293) cells to 82.36 ± 1.76% at an optimum dose of 100 µg/ml. Levels of hypoxia inducible factor-1 alpha (HIF-1α) were modulated four-fold upon supplementation with CSF2. The results collectively evinced that the CSF extracts are substantially bioactive and could be effectively utilized as mycotherapeutics for multiple bioeffects.

The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin

Cordycepin is an adenosine derivative isolated from Cordyceps sinensis, which has been used as an herbal complementary and alternative medicine with various biological activities. The general anti-cancer mechanisms of cordycepin are regulated by the adenosine A3 receptor, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), and glycogen synthase kinase (GSK)-3β, leading to cell cycle arrest or apoptosis. Notably, cordycepin also induces autophagy to trigger cell death, inhibits tumor metastasis, and modulates the immune system. Since the dysregulation of autophagy is associated with cancers and neuron, immune, and kidney diseases, cordycepin is considered an alternative treatment because of the involvement of cordycepin in autophagic signaling. However, the profound mechanism of autophagy induction by cordycepin has never been reviewed in detail. Therefore, in this article, we reviewed the anti-cancer and health-promoting effects of cordycepin in the neurons, kidneys, and the immune system through diverse mechanisms, including autophagy induction. We also suggest that formulation changes for cordycepin could enhance its bioactivity and bioavailability and lower its toxicity for future applications. A comprehensive understanding of the autophagy mechanism would provide novel mechanistic insight into the anti-cancer and health-promoting effects of cordycepin.