Cordycepin is the major bioactive component extracted from Cordyceps militaris. In recent years, cordycepin has received increasing attention owing to its multiple pharmacological activities. This ...study reviews recent researches on the anti‐inflammatory effects and the related activities of cordycepin. The results from our review indicate that cordycepin exerts protective effects against inflammatory injury for many diseases including acute lung injury (ALI), asthma, rheumatoid arthritis, Parkinson's disease (PD), hepatitis, atherosclerosis, and atopic dermatitis. Cordycepin regulates the NF‐κB, RIP2/Caspase‐1, Akt/GSK‐3β/p70S6K, TGF‐β/Smads, and Nrf2/HO‐1 signaling pathways among others. Several studies focusing on cordycepin derivatives were reviewed and found to down metabolic velocity of cordycepin and increase its bioavailability. Moreover, cordycepin enhanced immunity, inhibited the proliferation of viral RNA, and suppressed cytokine storms, thereby suggesting its potential to treat COVID‐19 and other viral infections. From the collected and reviewed information, this article provides the theoretical basis for the clinical applications of cordycepin and discusses the path for future studies focusing on expanding the medicinal use of cordycepin. Taken together, cordycepin and its analogs show great potential as the next new class of anti‐inflammatory agents.
As a valuable medicinal and edible fungus,
has been industrialized with broad development prospects. It contains a lot of bioactive compounds that are beneficial to our health. However, during ...artificial cultivation, strain degeneration is a challenge that inhibits the industrialization utility of
. Exogenous melatonin (MT) can scavenge for reactive oxygen species (ROS) in fungus and can alleviate strain degeneration. To establish the significance and molecular mechanisms of MT on strain degeneration, we investigated the third-generation strain (W5-3) of
morphological, biochemical, and transcriptomic approaches under MT treatment. Morphological analyses revealed that colony angulation of
was significantly weakened, and the aerial hypha was reduced by 60 μmol L
MT treatment. Biochemical analyses showed low levels of ROS and malondialdehyde (MDA), as well as increasing endogenous MT levels as exogenous MT increased. RNA-Seq revealed that compared with the control, several antioxidant enzyme-related genes were up-regulated under 60 μmol L
MT treatment. Among them,
genes were up-regulated by a factor of 11.04. In addition, genes that are potentially involved in cordycepin, adenosine and active compound biosynthesis for the growth and development of mycelium were up-regulated. Collectively, these findings provide the basis for further elucidation of the molecular mechanisms involved in
strain degeneration.
Cytotoxic nucleoside analogues were the first chemotherapeutic agents for cancer treatment. Cordycepin, an active ingredient of the insect fungus Cordyceps militaris, is a category of compounds that ...exhibit significant therapeutic potential. Cordycepin has many intracellular targets, including nucleic acid (DNA/RNA), apoptosis and cell cycle, etc. Investigations of the mechanism of anti-cancer drugs have yielded important information for the design of novel drug targets in order to enhance anti-tumor activity with less toxicity to patients. This extensive review covers various molecular aspects of cordycepin interactions with its recognized cellular targets and proposes the development of novel therapeutic strategies for cancer treatment.
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Cordyceps is a rare naturally occurring entomopathogenic fungus usually found at high altitudes on the Himalayan plateau and a well-known medicinal mushroom in traditional Chinese medicine. Cordyceps ...contains various bioactive components, out of which, cordycepin is considered most vital, due to its utmost therapeutic as well as nutraceutical potential. Moreover, the structure similarity of cordycepin with adenosine makes it an important bioactive component, with difference of only hydroxyl group, lacking in the 3′ position of its ribose moiety. Cordycepin is known for various nutraceutical and therapeutic potential, such as anti-diabetic, anti-hyperlipidemia, anti-fungal, anti-inflammatory, immunomodulatory, antioxidant, anti-aging, anticancer, antiviral, hepato-protective, hypo-sexuality, cardiovascular diseases, antimalarial, anti-osteoporotic, anti-arthritic, cosmeceutical etc. which makes it a most valuable medicinal mushroom for helping in maintaining good health. In this review, effort has been made to bring altogether the possible wide range of cordycepin’s nutraceutical potential along with its pharmacological actions and possible mechanism. Additionally, it also summarizes the details of cordycepin based nutraceuticals predominantly available in the market with expected global value. Moreover, this review will attract the attention of food scientists, nutritionists, pharmaceutical and food industries to improve the use of bioactive molecule cordycepin for nutraceutical purposes with commercialization to aid and promote healthy lifestyle, wellness and wellbeing.
Cerebral ischemia impairs physiological form of synaptic plasticity such as long-term potentiation (LTP). Clinical symptoms of cognitive dysfunction resulting from cerebral ischemia are associated ...with neuron loss and synaptic function impairment in hippocampus. It has been widely reported that cordycepin displays neuroprotective effect on ameliorating cognitive dysfunction induced by cerebral ischemia. Therefore, it is necessary to study whether cordycepin recovers cognitive function after brain ischemia through improving LTP induction. However, there has been very little discussion about the effects of cordycepin on LTP of cerebral ischemia so far. In the present study, we investigated the effects of cordycepin on LTP impairment and neuron loss induced by cerebral ischemia and excitotoxicity, using electrophysiological recording and Nissl staining techniques. The models were obtained by bilateral common carotid artery occlusion (BCCAO) and intrahippocampal NMDA microinjection. We also explored whether adenosine A1 receptors involve in the neuroprotection of cordycepin by using western blot. We found that cordycepin remarkably alleviated LTP impairment and protected pyramidal cell of hippocampal CA1 region against cerebral ischemia and excitotoxicity. Meanwhile, cordycepin prevented the reduction on adenosine A1 receptor level caused by ischemia but did not alter the adenosine A2A receptor level in hippocampal CA1 area. The improvement of LTP in the excitotoxic rats after cordycepin treatment could be blocked by DPCPX, a selective antagonist of adenosine A1 receptor. In summary, our findings provided new insights into the mechanisms of cordycepin neuroprotection in excitotoxic diseases, which is through regulating adenosine A1 receptor to improve LTP formation and neuronal survival.
Natural medicines for the treatment of fatigue: Bioactive components, pharmacology, and mechanisms
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It is a common phenomenon that people are in a sub-health condition and facing ...“unexplained fatigue”, which seriously affects their health, work efficiency and quality of life. Meanwhile, fatigue is also a common symptom of many serious diseases such as HIV/AIDS, cancer, and schizophrenia. However, there are still no official recommendations for the treatment of various forms of fatigue. Some traditional natural medicines are often used as health care products, such as ginseng, Cordyceps militaris (L.ex Fr.Link) and Rhodiola rosea L., and these have been reported to have specific anti-fatigue effects with small toxic and side effects and rich pharmacological activities. It may be promising treatment strategy for sub-health. In this review, we first outline the generation of fatigue. Furthermore, we put emphasis on the anti-fatigue mechanism, bioactive components, and clinic trials of natural medicines, which will contribute to the development of potential anti-fatigue agents and open up novel treatments for sub-health.
is a genus of ascomycete fungi that has been used for traditional herbal remedies. It contains various bioactive ingredients including cordycepin. Cordycepin, also known as 3-deoxyadenosine, is a ...major compound and has been suggested to have anticancer potential. The treatment of various cancer cells with cordycepin in effectively induces cell death and retards their cancerous properties. However, the underlying mechanism is not fully understood. Recent evidence has shed light on the molecular pathways involving cysteine-aspartic proteases (caspases), mitogen-activated protein kinases (MAPKs), and glycogen synthase kinase 3 beta (GSK-3β). Furthermore, the pathways are mediated by putative receptors, such as adenosine receptors (ADORAs), death receptors (DRs), and the epidermal growth factor receptor (EGFR). This review provides the molecular mechanisms by which cordycepin functions as a singular or combinational anticancer therapeutic agent.
Cordycepin is the major constituent of
Cordyceps
mushroom (or
Cordyceps militaris
) with therapeutic potential. Insects are the direct sources of nutrients for
Cordyceps
in nature. Therefore, ...optimized condition of
Cordyceps
cultivation for efficient cordycepin production was explored using six edible insects as substrates. The highest yield of cordycepin was produced by the cultivation on
Allomyrina dichotoma
and was 34 times that on
Bombyx mori
pupae. Among insect components, fat content was found to be important for cordycepin production. Especially, a positive correlation was deduced between oleic acid content and cordycepin production. The transcriptional levels of
cns1
and
cns2
, genes involved in cordycepin biosynthesis, were higher in
Cordyceps
grown on
A. dichotoma
than on other insects tested. The addition of oleic acid to the substrates increased cordycepin production together with the transcriptional levels of
cns1
and
cns2
. Therefore,
Cordyceps
with high content of cordycepin can be secured by the cultivation on insects.
•Enhancing therapeutic efficacy through the exploration of combination therapies involving immune checkpoint inhibitors is of paramount importance.•Recently, our research showcased the profound ...impact of a combination treatment involving cordycepin and the anti-CD47 antibody on tumor growth inhibition and extended lifespan in tumor-bearing mice.•In continuation, our present study successfully devised another combination therapeutic strategy incorporating cordycepin and CTLA-4 blockade, which demonstrated a remarkable synergistic effect against cancer.•To gain deeper insights into the underlying mechanisms, we conducted single-cell RNA sequencing and flow cytometry analyses to explore the remodeling of the tumor microenvironment, providing a comprehensive understanding of the intricate changes occurring at the cellular level.•These analyses illuminated the molecular interactions and immune modulation responsible for the observed therapeutic outcomes.
The strategy of using immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, leading to remarkable clinical outcomes. However, certain cancer types and patient demographics continue to face unique challenges. As a result, it is vital to investigate combination therapies that involve ICIs to boost therapeutic efficacy. Cordycepin, an adenosine derivative composed of adenine and pentose, holds immense promise for treating inflammation and cancer. Our recent research has demonstrated that the combined treatment of cordycepin and the anti-CD47 antibody significantly curtails tumor growth and extends the lifespan of tumor-bearing mice. In the current study, we showed that the combination of cordycepin and CTLA-4 blockade had a profound impact on suppressing tumor growth. We utilized the MC38 and CT26 tumor models to evaluate the therapeutic effect of cordycepin, CTLA-4 blockade, and their combined approach. Flow cytometry results unveiled that cordycepin, when combined with CTLA-4 blockade, considerably augmented the presence of tumor-infiltrating CD8+T cells and diminished the population of Foxp3+Tregs within the tumor microenvironment (TME). Additionally, we employed single-cell analysis to examine the TME’s reconfiguration upon the combined treatment of anti-CTLA-4 and cordycepin. We observed a significant impact on inhibiting tumor growth and substantially extended survival in tumor-bearing mice. Our data also demonstrated an increased proportion of effector CD8+T cells in the combined treatment group compared to all other groups, while exhausted CD8+T cells diminished in the combined group compared to the anti-CTLA-4 treatment alone. In conclusion, our findings supported the idea that combining cordycepin and CTLA-4 blockade could modify the effector and exhaustion status of CD8+T cells, thereby bolstering CD8+T-cell-mediated anti-tumor immunity in the TME. Collectively, our current study successfully established a combination therapeutic strategy utilizing cordycepin and CTLA-4 blockade. This strategy demonstrated a significant synergistic effect against cancer, highlighting its importance in cancer treatment.
Repeated-batch fermentation with fungal mycelia immobilized in plastic composite support (PCS) eliminates the lag phase during fermentation and improves metabolite productivity. The strategy is ...implemented herein, and a novel modified PCS is developed to enhance exopolysaccharide (EPS) production from the medicinal fungus Cordyceps militaris. A modified PCS (SYE + PCS) was made by compositing polypropylene (PP) with a nutrient mixture containing soybean hull, peptone, yeast extract, and minerals (SYE+). The use of SYE + PCS has consistent cell productivity throughout the multiple fermentation cycles, which resulted in a more higher cell productivity after second batch compared to unmodified PCS. The cell grown on SYE + PCS also generates a higher yield of EPS (3.36, 6.93, and 5.72 g/L in the first, second, and third fermentation cycles, respectively) up to three-fold higher than the cell immobilized on unmodified PCS. It is also worth noting that the EPS from mycelium grown on SYE + PCS contains up to 2.3-fold higher cordycepin than those on unmodified PCS. The presence of nutrients in SYE + PCS also affects the hydrophobicity and surface roughness of the PC, improving mycelial cell adhesion. This study also provides a preliminary antioxidant activity assessment of EPS from immobilized C. militaris grown with SYE + PCS.
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•Nutrient-enriched PCS tubes are used for immobilizing the C. militaris mycelial cell.•PCS with higher surface hydrophilicity is more favorable for cell adhesion.•Repeated-batch fermentation combined with cell immobilization can stimulate EPS production.•Highest EPS yield of 6.93 g/L is obtained in the second cycle of repeated-batch fermentation.•C. militaris EPS shows potential antioxidant properties and good biocompatibility.
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