The Pharmaceutical Potential of Cordyceps: Unlocking Nature's Treasure

Introduction

The naturally occurring caterpillar fungus, Ophiocordyceps sinensis, belonging to the Cordycipitaceae family, has been gathered for centuries in the Indian Himalayan regions and utilized as traditional medicine by the affluent and royalty. In contrast, Cordyceps militaris, another member of the same family, has been artificially cultivated for many years due to its simpler cultivation process, higher cordycepin content and notably lower cost compared to the original caterpillar fungus. Ophiocordyceps sinensis, with its limited natural availability, is considered the most expensive fungus globally, priced at around INR 30,00,000 (USD 35,957) per kilogram. Despite a slight decrease in price over the past few years, it remains unaffordable for a majority of the global population. Currently, there are no regulations governing the pricing of this mushroom. In India, the retail price typically ranges from INR 30,000 to 3,00,000 (USD 360 to 3,600) per kilogram of the dried fruiting body, with variations based on cultivation source, cordycepin content, cultivation costs, drying and storage methods, brand, and other factors.

Cordyceps militaris is a remarkable natural gift that can be cultivated in laboratory settings without losing its medicinal properties. Rich in pharmacologically potent molecules such as cordycepin, cordycepic acid, adenosine, and polysaccharides, this fungus has demonstrated various beneficial properties including anticancer, antioxidant, anti-aging, immunomodulatory, antidiabetic, antibacterial, antifungal, antiviral effects, enhancement of male fertility, and more. Serving as the most potent adaptogen in nature, regular consumption of it can significantly enhance both physical and mental well-being.

Cordyceps militaris: The Plethora of Nutraceuticals

The genus Cordyceps, which includes Cordyceps militaris, is known for containing various exceptional biomolecules with significant pharmaceutical potential, with cordycepin being the most prominent. Additionally, this mushroom and its mycelia are abundant in antioxidants, anti-cancer agents, fibrinolytic enzymes, antimicrobial compounds, adaptogens, immunomodulators, and more. Extensive research conducted over many years has led to the discovery of numerous unique pharmaceutical molecules within Cordyceps, which, either individually or in combination with others, play a harmonizing role in promoting overall physical and mental well-being.

A summary of bioactive components from Cordyceps militaris with their biological activities and implication in therapeutics is tabulated below.

Bioactive Compounds	Biological activity / Therapeutic effects
Cordycepin	Antitumor, anti-diabetic, anti-inflammatory, antimicrobial, inhibit platelet aggregation, hypolipidemic, analgesic, immunomodulatory
Adenosine	Anticonvulsant, Anti-inflammatory, Anti-tumor
Exopolysaccharide Fraction (EPSF)	Anti-tumor, antioxidant, anti-inflammatory, Immunomodulatory
Acid polysaccharides (APS)	Antioxidant, Immunomodulatory effect
CPS-1	Antioxidant
CPS-2	Cell proliferation inhibition
Mannoglucan	Cytotoxicity activity
CME-1	Antioxidant
PS-A	Inhibitory activity against cholesterol esterase
PS-A	Anti-tumor
D-mannitol (Cordycepic acid)	Diuretic, anti-tussive and anti-free radical activities
Ergosterol	Antimicrobial, antiviral, anti-arrhythmic effects, Helps in bone development
beta-Sitosterol	Protect from breast, colon and prostate cancer
H1-A	Immunoregulation
CSDNase	DNA hydrolysis, nucleolytic properties
CSP	Fibrinolytic activity
Cordymin	Anti-diabetic effect, antifungal
Cordycedipeptide A	Cytotoxic activity
Cordyceamides A and B	Cytotoxic activity
Tryptophan	Serves as precursor for the synthesis of the neurotransmitter?s serotonin and tryptamine
Xanthophylls	Anticancer
Fibrnolytic enzyme	Treatment of thrombosis
Proteoglucans	Enhanced anticancer effect on bladder cancer cells
Phenolic compounds	Antioxidant, antimicrobial, anti-arthritic, anti-carcinogenic, anti-hypertensive, cardio-protective, anti-inflammatory and anti-allergic
N-acetylgalactosamine	Necessary for intercellular communication
Exopolysaccharides, Chitinase, macrolides, cicadapeptins, myriocin, superoxide dismutase, protease, napthaquinone, Cordyheptapeptide and dipicolinic acid	Nutraceutical, pharmaceutical
B1	Essential in neurologic activities
B2	Helps in energy production
B12	Help in cellular metabolism, DNA synthesis, methylation and mitochondrial metabolism
E	Antioxidant, help in formation of blood cells, muscles, lung and nerve tissues, Increase immunity
K	Essential for blood clotting

Nutrient Profile of Cordyceps militaris

The fruiting body and mycelia of Cordyceps militaris are rich in proteins, unsaturated fatty acids, vitamins and mineral.

The nutrient profile of the mycelia and fruiting body of Cordyceps militaris is tabulated below. Note that the the nutrient composition may vary depending in the strain, substrate composition, incubation conditions and duration, mode of drying, storage, etc.

Nutrient Profile	Mycelia	Fruiting Body
Cordycepin	1.74 - 1.82 mg / g	1.10 - 10.28 mg/ g
D-mannitol (Cordycepic acid)	5.2 mg / kg	4.7 mg / kg
Ergothioneine	130.6 mg/ kg	782.3 mg/ kg
GABA	68.6 - 180.1 mg/ kg	756.30 ug / g
Lovastatin	37.7 - 57.3 mg / kg	2.76 ug / g
Vit A (Retinol)	100 mg/ kg	96 mg/ kg
Vit E (Tocopherols)	1.3 mg/ kg	3.6 mg/kg
Vit B2 (Riboflavin)	0.32 mg/ kg	0.16 mg/ kg
Vit B3 (Niacin)	1.2 mg/ kg	4.9 mg/ kg
Vit C (Ascorbic acid)	Not Detected	< 2 mg/ kg
Total amino acids (mg/ g)	24.98	57.39
Calcium	11 mg/kg	797 mg/kg
Potassium	12183 mg/ kg	15938 mg/ kg
Sodium	1567 mg/kg	171 mg/kg
Phosphorus	14293 mg/kg	7196 mg/kg
Magnesium	3414 mg/ kg	4227 mg/ kg
Sulphur	2558 mg/ kg	5088 mg/ kg
Selenium	< 0.5 mg/ kg	0.4 mg/ kg
Iron	9 mg/ kg	31 mg/ kg
Calcium	11 mg/ kg	797 mg/ kg
Zinc	10 mg/ kg	Not Detected
Protein	39.5%	59.8%
Fat	2.2%	8.8%
Carbohydrate	39.6%	29.1%
Energy (kcal/ 100 g)	336	401

Health Benefits of Cordyceps militaris i.e. Keeda Jadi Mushroom

By acting as the most potent natural adaptogen, Cordyceps militaris helps to balance the body's physiological and psychological state, promoting overall well-being.

It enhances and supports both our innate and adaptive immunity, aiding in the defense against various types of infections caused by viruses, bacteria, fungi, protozoa, and other microbes. It regulates the immune system to reduce inflammation, allergies, and certain autoimmune conditions.

Its medicinal properties include anti-diabetic and anti-lipidemic effects, which can help manage diabetes, hyperlipidemia, and related complications. It boosts the body's oxygen levels, enhancing aerobic performance and sustaining energy levels throughout the day. Additionally, it provides protective benefits for organs such as the liver, kidneys, lungs, and other glands. Ongoing research is likely to uncover more health advantages associated with Cordyceps militaris. Below are some of the health benefits attributed to consuming this natural supplement.

Health Benefits of Cordyceps militaris Mushroom

1. Antibiotic free remedy of Common Cold

For even a severe case of the common cold (including symptoms like cough, bronchitis, runny nose, teary eyes, sore throat, congestion, and difficulty breathing), consuming a single cup of tea can alleviate approximately 25% of the symptoms within one hour - making it one of the most powerful natural remedies for relieving the common cold!

Typically, the common cold will subside within 2-3 days.

It also effectively manages nighttime coughing starting from the first day.

2. Respiratory Health

Prevents common cold, Asthma and Pneumonia incidences

Ameliorates SARS, Influenza and common cold infections

Alleviates Asthma, Chronic Bronchitis, etc.

Increases O2 uptake, ventilation and aerobic performances

Relieves allergic Cough, Sneeze, Running nose, etc.

May alleviates silica-induced pulmonary inflammation and fibrosis.

3. Improves Cardiovascular Health, Anti-obesity

Corrects arrhythmic cardia (abnormal heart rate), bradycardia (slower heart rate) and tachycardia (faster heart rate).

Prevents blood vessel blockage by exerting Antiplatelet effects

Inhibits ceramide biosynthesis and attenuates metabolic impairments of obesity, diabetes and associated cardiovascular disease. 

Decreases total cholesterol, triglyceride, LDL-cholesterol simultaneously with increasing HDL-cholesterol.

Hypocholesterolemic, Hypotensive and Vasorelaxation Activities

4. Digestive Health

Enhances proliferation of probiotics and phenolic acid abundance in gut.

Modulates the intestinal barrier function and gut microbiota, which may provide a new strategy for improving intestinal health.

Alleviate inflammatory bowel diseases (IBD) and other gastrointestinal conditions by reducing gut inflammation.

Stimulates the production of digestive enzymes, thus improving digestion of food and subsequent absorption of nutrients.

5. Anti-diabetic, Hypoglycemic

Ameliorate type 2 diabetes mellitus by modulating the gut microbiota and metabolites.

Improves and repairs the impaired islet cells in pancreatic tissue.

Increases fasting serum insulin.

Decreases fasting body glucose (hypoglycemic), blood glycosylated Hb and homeostasis model assessment-insulin resistance.

Attenuated high glucose-induced cell damage, inflammation and abnormal energy metabolism.

May prevent diabetic nephropathy (chronic kidney disease).

6. Organoprotective

Promotes osmoregulation and hemopoietic functions.

Relieves fibrosis of Liver, Kidney, Lungs, Pancreas, etc.

Protects Liver, Kidney, Lungs, etc. from inflammation, toxicities and oxidative damages and improves their functioning.

Relieve fibrosis in the lung by inhibiting TGF-b1 expression and promotion of collagen degradation.

Lowered serum uric acid in blood of experimental mice.

7. Promotes Skin Health, may alleviate Acne 

Exhibits efficacy against some Skin Pathogenic Bacteria including Staphylococcus aureus, Pseudomonas aeruginosa, Cutibacterium acnes and methicillin-resistant S. aureus (MRSA).

Down-regulate the mecA gene expression in MRSA.Promotes overall skin health

May alleviate acne by inhibiting growth of Cutibacterium acnes.

Promotes wound healing, may lighten scar tissues.

8. Bidirectional Immunomodulator

Promotes the adaptive immune system, including cellular and humoral immunity

Acts as a  bidirectional modulator with both potentiating and suppressive effects on the immune system through regulating innate and adaptive immunity.

May control autoimmune disorders and graft rejections.

Anti-allergic, minimizes inflammation of Tissues and Organs.

Anti-arthritic, anti-asthmatic

Ameliorates experimental autoimmune encephalomyelitis by inhibiting leukocyte infiltration and reducing neuroinflammation.

9. Anti-inflammatory 

Reduces pulmonary inflammations in various respiratory diseases such as asthma, acute respiratory distress syndrome, cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).

Improves mucus clearance and airway surface hydration.

Minimizes inflammation of tissues and organs.

Downregulates outcomes of allergic reactions.

10. Antioxidant, Antiaging, Anxiolytic

Slows down aging of organs and body

Scavenges Reactive Oxygen Species (ROS)

Minimizes oxidative damage of Nucleic acids, Lipids, proteins, etc.

Minimizes lipid peroxidation

Busts stress and improves sleep pattern.

11. Boosts Energy & Oxygenation 

Improves performance of Aerobic Exercise

Boosts Energy Level, Delays Fatigue

Most potent natural Adaptogen

Promotes Overall Wellness

12. Neurotropic & Neuroprotective

Improves cognitive performance, Reverses memory impairment, improves dementia.

Promotes neuron growth and functions.

Prevents neuropathy of Diabetes.

May improves cognitive performance in Autism.

Cordycepin confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury.

13. Broad spectrum Antimicrobial

Broad spectrum antibacterial, antiviral, insecticidal, larvicidal and antiparasitic

Fights viral infections (Influenza, SARS, Dengue, HIV 1, etc.).

Inhibits protein and nucleic acid synthesis of Plasmodium (c.a. of Malaria)

Cordycepin Inhibits Virus Replication in Dengue Virus-Infected Vero Cells

Cordycepin Inhibits Replication of Enterovirus A71 (EV-A71), the causative agent of hand-foot-and-mouth disease (HFMD).

Cordycepin kills Mycobacterium tuberculosis through hijacking the bacterial adenosine kinase.

14. Reproductive Health

Increases sperm concentrations and ratio of motile sperm.

Improves libido by boosting acting as aphrodisiac, anti-fatigue, anti-depressant and promoting hormonal balance.

Improves fertility in both sexes.

Aphrodisiac

15. Anti-Covid

The only molecules on this Earth to neutralize SARS-CoV2 virus by targeting 1. Spike protein, 2. Main protease, 3. RNA dependent RNA polymerase, as well as 4. acting as Adenosine analog. Reduces inflammation of respiratory system.

Increases O2 uptake, ventilation and aerobic performances.

Kills SARS-CoV2 virus and develops immunity.

16. Anti-Hyperuricemic

Lowered serum uric acid in blood of experimental mice.

May alleviate gout, renal sicknesses, hypertension, hyperlipidemia, and atherosclerosis. 

17. Cordycepin Inhibits Virus Replication in Dengue Virus-Infected Vero Cells

Dengue virus (DENV) infection causes mild to severe illness in humans that can lead to fatality in severe cases.

Currently, no specific antiviral treatment available for Dengue virus.

18. Cordycepin Inhibits Replication of Enterovirus A71 (EV-A71)

EV-A71 causes hand-foot-and-mouth disease (HFMD), generally a mild illness but occasionally leads to severe or fatal neurological complications in infants and young children.

Currently, no specific antiviral treatment available for AV-A71

19. Treatment of Tuberculosis

Cordycepin kills Mycobacterium tuberculosis through hijacking the bacterial adenosine kinase. Can be used as adjuvant in TB treatment

 20. Anti-tumor and anti-cancer

Antiproliferative effect various tumor cell lines.

Accelerates the Kupffer cells mediated phagocytosis to prevent metastasis.

Stronger antitumor activity against MCF-7, B16, HL-60, and HepG2 cancer cell lines. Apoptosis and autophagy of various types of cancer cells.Restrains the proliferation of cancer cells and angiogenesis in solid tumors.

I. As an adjuvant enhances the chemosensitivity of gall bladder cancer cells

II. Cordycepin enhances the chemosensitivity of esophageal cancer cells to cisplatin by inducing the activation of AMPK and suppressing the AKT signaling pathway.

III. Compared with conventional treatment, adjuvant treatment with Cordyceps sinensis of lung cancer not only improve TRR, QOL and immune function, but also reduce the incidence of ADRs and radiation pneumonitis.

IV. Cordyceps militaris Exerts Antitumor Effect on Carboplatin-Resistant Ovarian Cancer via Activation of ATF3/TP53 Signaling.

V. Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity.

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