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Pharmacological basis of 'Yin-nourishing' and 'Yang-invigorating' actions of Cordyceps, a Chinese tonifying herb
Abstract
Cordyceps sinensis (Berk.) Sacc. (Cordyceps), a popular Chinese tonifying herb, was revered for being both 'Yin-nourishing' and 'Yang-invigorating' in Chinese medicine. In order to establish the pharmacological basis for the 'Yin-nourishing' and 'Yang-invigorating' action of Cordyceps, the effects of wild and cultured Cordyceps on concanavalin A (Con A)-stimulated splenocytes, an in vitro bioassay for 'Yin-nourishment', and myocardial ATP generation capacity, an ex vivo bioassay for 'Yang-invigoration', were investigated in mice. The results indicated that methanolic extracts of wild and cultured Cordyceps enhanced both the Con A-stimulated splenocyte proliferation in vitro and myocardial mitochondrial ATP generation ex vivo in mice, with no significant difference in potency of action between the two types of Cordyceps. While the immuno-potentiating effect was associated with the increase in interleukin II production, the stimulation of myocardial ATP generation was paralleled by an enhancement in mitochondrial electron transport. When compared with typical 'Yin' and 'Yang' tonifying Chinese herbs, Cordyceps was found to possess both 'Yin-nourishing' and 'Yang-invigorating' activities, with a lower potency in both modes of action. The pharmacological characterization of Cordyceps by means of contemporary bioassays is consistent with the time-honored clinical observation from Chinese herbalists.
... Cordyceps encourages the adaptive immune system. Although natural and cultured yarsaghumba methanol extracts had no proliferation of primary mouse splenocytes in vitro [210] or mice in vivo [207]; the extracts improved stimulated proliferation of mouse splenocytes in vitro [210] or ovalbumin-induced proliferation and serum immunoglobulin in immunized mice [211]. Cultured C. Sinensis increased CD25 appearance on lymphocytes in vitro [207], help patients with posthepatic cirrhosis [196]. ...
... Cordyceps encourages the adaptive immune system. Although natural and cultured yarsaghumba methanol extracts had no proliferation of primary mouse splenocytes in vitro [210] or mice in vivo [207]; the extracts improved stimulated proliferation of mouse splenocytes in vitro [210] or ovalbumin-induced proliferation and serum immunoglobulin in immunized mice [211]. Cultured C. Sinensis increased CD25 appearance on lymphocytes in vitro [207], help patients with posthepatic cirrhosis [196]. ...
... The Pharma Innovation Journal http://www.thepharmajournal.com released which is further utilized by the cell (Dai et al. 2001;Siu et al. 2004) [20,82] . ...
... The Pharma Innovation Journal http://www.thepharmajournal.com released which is further utilized by the cell (Dai et al. 2001;Siu et al. 2004) [20,82] . ...
This review mainly focuses on the medicinal value of the Cordyceps sinensis. Interestingly, Cordyceps
spp. contains different compounds with the ability to strengthen the response of the immune system and
also to control its exacerbated response. Most of the information on the effect of Cordyceps on the
immune system derives from studies in cancer. Upholding immunity and strong immune system are
prime concern especially during microbial infections as in the case of current COVID-19 pandemic. This
is a mushroom that is only found in cohabitation with the larvae of an insect, and it is this unique growth
parameter that has made it challenging to produce Cordyceps spp. in artificial cultivation. Further
complicating this cultivation issue is the rarefied atmosphere, mineral-rich soil, and low temperature in
which Cordyceps naturally grows, resulting in a unique profile of secondary metabolites possessing
interesting biological potential for medical exploitation, but which are not readily reproduced in normal
laboratory cultivation. In this article, we attempt to unravel many of the mysteries of Cordyceps spp.,
with special attention to C. sinensis, the world's most costly medicinal mushroom.
Keywords: Cordyceps sinensis, caterpillar mushroom, immuno-booster, medicinal properties, nutritional
composition
... It seemed that biocompounds isolated from fungus grown in bioreactors poses a wide spectrum of biological activity to that of naturally-collected Cordyceps. Previous studies on Cordyceps have showed it to possess antibacterial, antifungal, larvacidal, anti-inflammatory, antidiabetic, antioxidant, antitumor, prosexual, apoptotic and immunomodulatory activities [31,[56][57][58][59][60][61][62]. Administration of Cordyceps may be able to improve movement, relieve fatigue, lower high cholesterol, dilate blood vessels, calm the body, prevent and treat infertility and impotence as well as improve strength; it may also be effective against ome symptoms of HIV/AIDS [11,31,[56][57][58][59][60][61][62]. ...
... Previous studies on Cordyceps have showed it to possess antibacterial, antifungal, larvacidal, anti-inflammatory, antidiabetic, antioxidant, antitumor, prosexual, apoptotic and immunomodulatory activities [31,[56][57][58][59][60][61][62]. Administration of Cordyceps may be able to improve movement, relieve fatigue, lower high cholesterol, dilate blood vessels, calm the body, prevent and treat infertility and impotence as well as improve strength; it may also be effective against ome symptoms of HIV/AIDS [11,31,[56][57][58][59][60][61][62]. The caterpillar fungus Ophiocordyceps sinensis is promoted as a natural Viagra [49]. ...
The aim of the presented mini-review is to review the literature data referring to opportunistic mycoses in pet dogs and cats suffering from other concurrent diseases, comparable to human medical disorders with high risk of secondary mycoses. This review also presents the preliminary results of a project aimed at understanding the fungal colonization and occurrence of secondary mycoses in pets suffering from metabolic disorders, neoplasms and viral infections. The incidence of opportunistic mycoses is higher in such individuals, mostly because of their impaired immunity. The main risk factors are primary and secondary types of immunodeficiency connected with anti-cancer treatment or neoplastic disease itself. Moreover, literature data and the results of our investigations show that Candida yeasts are prevalent among diabetic animals and indicate that these fungi are the main etiological agents of secondary infections of the oral cavity, GI and urogenital tracts. Other important conditions possibly favoring the development of mycoses are concurrent infections of cats with FeLV and FIV viruses. Thus, in all cases of the mentioned underlying diseases, animals should be carefully monitored by repeated mycological examination, together with inspection of other parameters. Also, the prophylaxis of opportunistic mycoses should be carefully considered alike other factors influencing the prognosis and the outcome of primary diseases.
... The parasitic complex of the fungus and the caterpillar are found in the soil of a prairie at an elevation of 3500-5000 m. According to Chinese medicinal theory, Cordyceps processes both "Yin-nourishing" and "Yang-invigorating" activities (Siu et al., 2004). Indeed, different therapeutic purposes of Cordyceps have been reported, which include stimulation of immune response; inhibition of cancer growth; protection of kidney and liver; stimulation of cardiovascular circulation; lowering blood glucose; and against free-radical formation (Zhu et al., 1998a,b;Li and Tsim, 2004). ...
... This notion was supported by (i) the phosphorylation of ERK1/2 was triggered by the application of cordysinocan, and (ii) the cordysinocan-induced T-lymphocyte proliferation was blocked by the ERK inhibitor. Besides our current studies as shown here, the immuno-modulation activity of UST2000 has also been revealed by antoher group that the methanolic extract of this culture Cordyceps could enchance the Con A-stimulated spenocyte proliferation as well as the production of IL-2 (Siu et al., 2004). These findings are in accordance with the study that polysaccharide is a key immuno-stimulating component of Cordyceps. ...
Cordyceps sinensis, a well-known traditional Chinese medicine, possesses activities in anti-tumor, anti-oxidation and stimulating the immune response; however, the identity of active component(s) is not determined. A strain of Cordyceps sinensis, namely UST 2000, has been isolated. By using activity-guided purification, a novel polysaccharide of molecular weight approximately 82 kDa was isolated from the conditioned medium of cultured Cordyceps. The isolated exo-polysaccharide, namely cordysinocan, contains glucose, mannose, galactose in a ratio of 2.4:2:1. In cultured T-lymphocytes, application of cordysinocan induced the cell proliferation and the secretion of interleukin-2, interleukin-6 and interleukin-8. In addition, the phosphorylation of extracellular signal-regulated kinases (ERK) was induced transiently by the treatment of cordysinocan. Moreover, application of cordysinocan in cultured macrophages increased the phagocytosis activity and the enzymatic activity of acid phosphatase. These results therefore verify the important role of Cordyceps polysaccharide in triggering such immune responses.
... This fungus is commonly used as a functional food to reduce inflammation in the body, to improve respiratory system, libido and erectile function, and to treat liver, cardiovascular and chronic kidney diseases (3,4). It is also used as a type of herbal tonic to restore energy and promote general health (3,5). ...
Research background. Ophiocordyceps sinensis, a highly valued medicinal fungus, is close to extinction due to overexploitation. Successful cultivation of O. sinensis fruiting body (OCS02®) shows that the cultivar has a promising nutritional value and numerous bioactive compounds. Antioxidant and antiproliferative properties and biologically active proteins of the OCS02® are investigated for possible development into nutraceuticals.
Experimental approach. The chemical composition of the OCS02® cold water extract was determined, and the antioxidant activities were examined using ferric reducing, DPPH• and O2•- scavenging assays. Tetrazolium dye (MTT) cytotoxic assay was performed to assess the antiproliferative activity of the extract. Bioactive proteins in the active fraction of the extract were identified using liquid chromatography (LC) and tandem-mass spectrometry (MS/MS).
Results and conclusions. The OCS02® extract exhibited strong O2•- scavenging (expressed as Trolox equivalents (18.4±1.1) mol/g) and potent cytotoxic activities against adenocarcinomic human alveolar basal epithelial (A549) cells (IC50=(58.2±6.8) µg/mL). High molecular mass polysaccharides, proteins and protein-polysaccharide complexes could have contributed to the antioxidant and cytotoxic selectivity of the OCS02®. LC-MS/MS analysis identified several potential cytotoxic proteases and an oxalate decarboxylase protein which may exhibit protection effects on kidneys.
Novelty and scientific contribution. The findings demonstrate the potential of OCS02® to be developed into functional food due to its promising superoxide anion radical scavenging capacity, cytotoxic effect and presence of biopharmaceutically active proteins.
... Traditionally, it has been used as an herbal medicine in Korea and China, to enhance longevity and vitality. 19,20 A couple of well-known active ingredients in these mushrooms include cordycepin, cordycepic acid, sterols (ergosterol), nucleosides, and polysaccharides. 21 C militaris has been reported to exert immunomodulatory, anti-inflammatory, antimicrobial, and antitumor effects. ...
This study aimed to investigate the effect of Cordyceps militaris extract on the proliferation and apoptosis of non–small cell lung cancer (NSCLC) cells and determine the underlying mechanisms. We performed a CCK-8 assay to detect cell proliferation, detection of morphological changes through transmission electron microscopy (TEM), annexin V–FITC/PI double staining to analyze apoptosis, and immunoblotting to measure the protein expression of apoptosis and hedgehog signaling–related proteins, with C militaris treated NSCLC cells. In this study, we first found that C militaris reduced the viability and induced morphological disruption in NSCLC cells. The gene expression profiles indicated a reprogramming pattern of genes and transcription factors associated with the action of TCTN3 on NSCLC cells. We also confirmed that the C militaris–induced inhibition of TCTN3 expression affected the hedgehog signaling pathway. Immunoblotting indicated that C militaris–mediated TCTN3 downregulation induced apoptosis in NSCLC cells, involved in the serial activation of caspases. Moreover, we demonstrated that the C militaris negatively modulated GLI1 transcriptional activity by suppressing SMO/PTCH1 signaling, which affects the intrinsic apoptotic pathway. When hedgehog binds to the PTCH1, SMO dissociates from PTCH1 inhibition at cilia. As a result, the active GLI1 translocates to the nucleus. C militaris clearly suppressed GLI1 nuclear translocation, leading to Bcl-2 and Bcl-xL down-regulation. These results suggested that C militaris induced NSCLC cell apoptosis, possibly through the downregulation of SMO/PTCH1 signaling and GLI1 activation via inhibition of TCTN3. Taken together, our findings provide new insights into the treatment of NSCLC using C militaris.
... Cordyceps militaris (L.) Fr. is a species of fungus in the family Clavicipitaceae that has been a traditional potential harbour of bio-metabolites for herbal drugs in Korea and China for revitalization of various systems of the body including enhance of longevity and vitality [7,8]. It contains many kinds of active ingredients (such as cordycepin, cordycepic acid, sterols (ergosterol), nucleosides, and polysaccharides), and due to its various physiological activities, it is now used for multiple medicinal purposes [9]. ...
Background:
Cordyceps militaris (L.) Fr. (C. militaris) exhibits pharmacological activities, including antitumor properties, through the regulation of the nuclear factor kappa B (NF-κB) signaling. Tumor Necrosis Factor (TNF) and TNF-α modulates cell survival and apoptosis through NF- κB signaling. However, the mechanism underlying its mode of action on the NF-κB pathway is unclear.
Methods:
Here, we analyzed the effect of C. militaris extract (CME) on the proliferation of ovarian cancer cells by confirming viability, morphological changes, migration assay. Additionally, CME induced apoptosis was determined by apoptosis assay and apoptotic body formation under TEM. The mechanisms of CME were determined through microarray, immunoblotting and immunocytochemistry.
Results:
CME reduced the viability of cells in a dose-dependent manner and induced morphological changes. We confirmed the decrease in the migration activity of SKOV-3 cells after treatment with CME and the consequent induction of apoptosis. Immunoblotting results showed that the CME-mediated upregulation of tumor necrosis factor receptor 1 (TNFR1) expression induced apoptosis of SKOV-3 cells via the serial activation of caspases. Moreover, CME negatively modulated NF-κB activation via TNFR expression, suggestive of the activation of the extrinsic apoptotic pathway. The binding of TNF-α to TNFR results in the disassociation of IκB from NF-κB and the subsequent translocation of the active NF-κB to the nucleus. CME clearly suppressed NF-κB translocation induced by interleukin (IL-1β) from the cytosol into the nucleus. The decrease in the expression levels of B cell lymphoma (Bcl)-xL and Bcl-2 led to a marked increase in cell apoptosis.
Conclusion:
These results suggest that C. militaris inhibited ovarian cancer cell proliferation, survival, and migration, possibly through the coordination between TNF-α/TNFR1 signaling and NF-κB activation. Taken together, our findings provide a new insight into a novel treatment strategy for ovarian cancer using C. militaris.
... Cordyceps sinensis is a popular tonify Chinese medicine with strong anti-fatigue effects [16,21]. It was reported that Cordyceps extracts treatment for 3 days enhanced myocardial ATP generation capacity ex vivo in mice by around 30 % [22], suggesting the potential role of cordyceps in cellular energy supply. During cerebral ischemia, lack of oxygen causes neuron's normal process for making ATP for energy to fail. ...
Corbrin Capsule is a traditional Chinese patent medicine with the main component of fermentative cordyceps fungus powder (Cs-C-Q80). The indications of Corbrin Capsule include chronic renal insufficiency, chronic obstructive pulmonary (COPD), pulmonary fibrosis, and chronic bronchitis. However, the effects of Corbrin Capsule on acute cerebral ischemia are still unclear. The objective of this study was to explore the preventive effect of Corbrin Capsule in permanent and transient middle cerebral artery occlusion (MACO) mice model. Male C57BL/6 mice were given Corbrin of 0.04, 0.2 and 1 mg/kg by gavage once a day for 3, 7 or 14 days and then subjected to pMCAO or tMCAO. Infarct volumes, neurological deficit score, ATP concentration, SOD activity and MDA content were assessed. Results showed that prolonged pretreatment with Corbrin (1.0 mg/kg) to 7 days or more effectively ameliorated brain infarct and neurological scores in pMCAO mice. Shorter (3 days) or without pretreatment of Corbrin was invalid, suggesting a pretreatment time window. The ATP concentration was significantly increased with effective Corbrin pretreatments in ischemic brains, while the content of MDA sharply decreased in Corbrin groups. In tMCAO mice, Corbrin showed no neuroprotection even with pretreatment. In conclusion, long-term pre-administration of Corbrin Capsule is necessary for its anti-cerebral ischemic effects, and the underlying mechanisms might be associated with increase of ATP concentration and the anti-inflammatory effects in ischemic brain tissue.
... 65 Doğal veya kültür yolu ile elde edilen Cordyceps ekstrelerinin (1 g/kg/gün) 3 gün boyunca uygulanması, tedavi edilen farelerde miyokardiyal ATP üretim kapasitesini, sırasıyla %29 ve %32 oranında artırmıştır. 66 C. sinensis'in sıcak su ekstresinin (500-2000 mg/kg) dışındaki süperkritik sıvı ekstresinin de (2,5-10 mL/kg) antidepresan aktivite gösterdiği belirtilmektedir. Cordyceps'in adrenerjik ve dopaminerjik sistemleri etkileyerek gösterdiği antidepresan etki de araştırılmaktadır. ...
... Cordyceps militaris is a genus of parasitic fungi. The extract of Cordyceps militaris (CME) has traditionally been used as an herbal medicine in Korea and China to enhance longevity and vitality [1,2]. Several of the well-known active ingredients of these mushrooms include cordycepin, cordycepic acid, sterols (ergosterol), nucleosides, and polysaccharides [3]. ...
The ubiquitous transcription factor, NF-κB, has been reported to inhibit apoptosis and induce drug resistance in cancer cells. Cordyceps militaris extract (CME) is involved in the regulation of the NF-κB signaling pathway. However, the detailed role of CME in the suppression of the NF-κB signaling pathway is unclear. We found that CME dose-dependently inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in TK-10 human renal cell carcinoma. CME prevented NF-κB from translocating to the nucleus, which resulted in the downregulation of GADD45B, upregulation of MKK7, and phosphorylation of JNK (p-JNK). The increased activation of Bax led to pronounced CME-induced apoptosis, which occurred through caspase-3. Furthermore, the siRNA-mediated knockdown of GADD45B inhibited MKK7 expression, whereas the siRNA-mediated inhibition of MKK7 downregulated p-JNK and the JNK inhibitor, SP600125, inhibited Bax expression. Thus, these results indicated that CME inhibited the activation of GADD45B via the inhibition of NF-κB activation, which upregulated the MKK7-JNK signaling pathway to induce apoptosis in TK-10 cells. Thus, this study reveals a novel anticancer function of CME.
... With Cordyceps at their disposal, they were able to trek higher into the mountains and stay there for longer periods of time. We now think that one of the reasons for this energy-boosting effect is this increase of cellular ATP (Siu et al. 2004). In addition to increasing cellular ATP, recent studies have shown that oxygen availability is facilitated from taking Cordyceps (Hirsch et al. 2017), which would also help to explain how Cordyceps assists in these high-altitude jaunts. ...
Traditional Chinese medicine (TCM) has a long history of using plant, animal, and fungal materials for their medicinal values. One of the better known and by far the most expensive of the Oriental medicines is the family of fungal-insect pairings known as Cordyceps. Different Cordyceps species, most notably Ophiocordyceps sinensis, have a long history of use and have been found growing only from the head of a subterranean caterpillar above 3000 m altitude on the Qinghai-Tibetan plateau. Environmental and ecological factors have driven O. sinensis to the status of an endangered species, with annual harvests steadily declining while at the same time the worldwide demand is ever increasing. This has driven the prices for O. sinensis into an ever-increasing spiral over the last decade, with top-quality Cordyceps currently valued at more than one hundred thousand US dollars per kilogram (100,000 USD) in the major Chinese cities. Its value today is literally higher than the price of gold. Such fantastic prices are driving research into cultivating O. sinensis and other Cordyceps species with an eye to making them more affordable for commercial trade. Aloha Medicinals in the United States is currently the largest cultivator of Cordyceps in the world producing an estimated half of all the Cordyceps annually consumed, but in addition to cultivating this rare fungus for the pharmaceutical trade, they are also involved in researching new species of Cordyceps from around the world with similar or identical medicinal properties as the classic species, O. sinensis. Recently, Aloha Medicinals expeditions into the Tingo Maria Valley in Peru have found that this area has the greatest diversity of Cordyceps species of any known location. More than 1000 types of Cordyceps have been found in Tingo Maria Valley so far, the vast majority of which have yet to be described or named. Currently, biotechnology companies around the world are cultivating about a dozen different species of Cordyceps for use in the pharmaceutical and nutraceutical sectors. With the discovery of the incredible diversity of entomogenous fungi in Peru, many new candidate species are now being researched for their medicinal properties and the potential for cultivation, in an effort to commercialization as substitutes for increasingly rare O. sinensis. As research continues to prove the wide range of medicinal properties claimed for Cordyceps, the potential for developing new medicinal Cordyceps species to replace the rare and endangered wild-collected O. sinensis has great potential.
... The caterpillar fungus has a hypoglycemic effect and may be beneficial for people with insulin resistance [140]. Owing to its diuretic effect, it is crucial for the prevention of nephralgia [141]. Additional attributes include the potential to adjust protein metabolism, inhibit lung carcinoma, replenish kidneys, attenuate renal fibrosis [124], soothe lungs [142], treat aging disorders [143], stimulate the production of corticosteroids [144] and improve blood circulation [1]. ...
Members of the entomophagous fungi are considered very crucial in the fungal domain relative to their natural phenomenon and economic perspectives; however, inadequate knowledge of their mechanisms of interaction keeps them lagging behind in parallel studies of fungi associated with agro-ecology, forest pathology and medical biology. Ophiocordyceps sinensis (syn. Cordyceps sinensis), an intricate fungus-caterpillar complex after it parasitizes the larva of the moth, is a highly prized medicinal fungus known widely for ages due to its peculiar biochemical assets. Recent technological innovations have significantly contributed a great deal to profiling the variable clinical importance of this fungus and other related fungi with similar medicinal potential. However, a detailed mechanism behind fungal pathogenicity and fungal-insect interactions seems rather ambiguous and is poorly justified, demanding special attention. The goal of the present review is to divulge an update on the published data and provides promising insights on different biological events that have remained underemphasized in previous reviews on fungal biology with relation to life-history trade-offs, host specialization and selection pressures. The infection of larvae by a fungus is not a unique event in Cordyceps; hence, other fungal species are also reviewed for effective comparison. Conceivably, the rationale and approaches behind the inheritance of pharmacological abilities acquired and stored within the insect framework at a time when they are completely hijacked and consumed by fungal parasites, and the molecular mechanisms involved therein, are clearly documented.
... Based on the classification of taste in traditional Chinese medicine, herbs with the same taste descriptor generally possess similar therapeutic properties, and herbs with different taste descriptors generally have different therapeutic properties [6]. For example, the so-called "sweet" class of herbs is associated with a tonic effect that can nourish the body, hence promoting a healthy status, boosting the immune system, and helping fight the aging process [4,7,8]. On the other hand, herbs in the so-called "pungent" class eliminate pathological agents and therefore treat the corresponding symptoms (e.g., stagnation) by promoting the circulation of energy and blood [4]. ...
... Biochemical analysis of O. sinensis revealed several active constituents including mannitol, nucleosides, ergosterol, aminophenol, and trace elements (11). Some polysaccharide components and cordycepin, which showed anticancer activity in preliminary in vitro and animal studies, have been isolated from O. sinensis (12). ...
Ophiocordyceps sinensis is a natural fungus that has been valued as a health food and used in traditional Chinese medicine for centuries. The fungus is parasitic and colonizes insect larva. Naturally occurring O. sinensis thrives at high altitude in cold and grassy alpine meadows on the Himalayan mountain ranges. Wild Ophiocordyceps is becoming increasingly rare in its natural habitat, and its price limits its use in clinical practice. Therefore, the development of a standardized alternative is a great focus of research to allow the use of Ophiocordyceps as a medicine. To develop an alternative for wild Ophiocordyceps, a refined standardized extract, CBG-CS-2, was produced by artificial fermentation and extraction of the mycelial strain Paecilomyces hepiali CBG-CS-1, which originated from wild O. sinensis. In this study, we analyzed the in vitro immune-modulating effect of CBG-CS-2 on natural killer cells and B and T lymphocytes. CBG-CS-2 stimulated splenocyte proliferation and enhanced Th1-type cytokine expression in the mouse splenocytes. Importantly, in vitro CBG-CS-2 treatment enhanced the killing activity of the NK-92MI natural killer cell line. These results indicate that the mycelial culture extract prepared from Ophiocordyceps exhibits immune-modulating activity, as was observed in vivo and this suggests its possible use in the treatment of diseases caused by abnormal immune function.
... In China, Cordyceps is often used as a tonic drug for patients with serious diseases. Recent scientific research shows Cordyceps has antioxidant (Ng & Wang, 2005), antitumour, immunomodulating, antihypertensive (Zhou et al., 2009) and hypoglycaemic effects (Ng & Wang, 2005) and enhances myocardial mitochondrial ATP generation (Siu et al., 2004). Polysaccharides and nucleosides are believed to be the main bioactive components responsible for the pharmacological effects. ...
... At the end of the culture period, the extent of splenocyte proliferation was determined by a colorimetric assay using MTT-based cell proliferation kit I. The extent of Con Astimulated proliferation of isolated splenocytes was estimated by computing the area under the curve (AUC) of the graph plotting the net absorbance (mean absorbance of cells stimulated with Con A-mean absorbance of cells not stimulated with Con A) against Con A concentration. The effect of IPP on the extent of Con A-stimulated proliferation was compared with that of the IPPuntreated control, and data were expressed as percent control [13]. ...
This study aimed to investigate the effects of a compound polysaccharide-based health product (Infinitus Polysac Plus, IPP) on innate and adaptive immunity in mice. Both ex vivo/in vivo mouse models and an in vitro system using cultured mouse splenocytes were adopted for the assessment of innate and adaptive immunity. For the innate immune response, long-term IPP treatment (0.26 and 0.78 g/kg * 20 doses) enhanced the carbon clearance activity and phagocytic rate of macrophages, as well as natural killer cell activity in mice. The IPP-induced increase in natural killer cell activity was accompanied by the suppression of tumor growth in Sarcoma-180 cell-inoculated mice. For the adaptive immune response, while long-term IPP treatment increased the splenocyte index in mice, IPP incubation with mouse splenocytes in vitro potentiated their concanavalin A-stimulated proliferation. Long-term IPP treatment significantly restored the hemolytic activity of serum on sheep red blood cells and dinitrofluorobenezene-induced delayed-type hypersensitivity in sensitized and immunosuppressed mice. In conclusion, the results indicate that long-term IPP treatment produces stimulatory effects on both innate and adaptive immunity in mice.
... At the end of the culture period, the extent of splenocyte proliferation was determined by a colorimetric assay using MTT-based cell proliferation kit I. The extent of Con Astimulated proliferation of isolated splenocytes was estimated by computing the area under the curve (AUC) of the graph plotting the net absorbance (mean absorbance of cells stimulated with Con A-mean absorbance of cells not stimulated with Con A) against Con A concentration. The effect of IPP on the extent of Con A-stimulated proliferation was compared with that of the IPPuntreated control, and data were expressed as percent control [13]. ...
This study aimed to investigate the effects of a compound polysaccharide-based health product (Infinitus Po-lysac Plus, IPP) on innate and adaptive immunity in mice. Both ex vivo/in vivo mouse models and an in vitro system using cultured mouse splenocytes were adopted for the assessment of innate and adaptive immunity. For the innate immune response, long-term IPP treatment (0.26 and 0.78 g/kg 20 doses) enhanced the car-bon clearance activity and phagocytic rate of macrophages, as well as natural killer cell activity in mice. The IPP-induced increase in natural killer cell activity was accompanied by the suppression of tumor growth in Sarcoma-180 cell-inoculated mice. For the adaptive immune response, while long-term IPP treatment in-creased the splenocyte index in mice, IPP incubation with mouse splenocytes in vitro potentiated their con-canavalin A-stimulated proliferation. Long-term IPP treatment significantly restored the hemolytic activity of serum on sheep red blood cells and dinitrofluorobenezene-induced delayed-type hypersensitivity in sensi-tized and immunosuppressed mice. In conclusion, the results indicate that long-term IPP treatment produces stimulatory effects on both innate and adaptive immunity in mice.
... Another important aspect is that the same herb can possess both Yin-nourishing and Yang-invigorating activities, e.g. Cordyceps sinensis (Siu et al, 2004;Li et al, 2009). Having a Yin-nourishing potential does not exclude the Yang invigorating capacity, which means antioxidant potential does not eliminate the stimulatory activity on the PMNL free radical generation. ...
One of the biggest obstacles to progress in traditional Chinese medicine (TCM) development in Western countries is the difficulty of applying the traditional concepts to the Western medicinal plants, which are not traditionally described in ancient literature. During recent years, new advances in the field of understanding Yin/Yang aspects from a modern bioscientific point of view have led to the conclusion that antioxidation-oxidation concepts might mirror a Yin-Yang relationship.
Methods: This study was intended to integrate the Yin-Yang theory of the traditional Chinese medicine with modern antioxidation-oxidation theory, and to propose a biochemical tool based on redox parameters (e. g. antioxidant capacity, chemiluminescence-CL signal inducing capacity), usable for the classification of Western medicinal plants from Yin/Yang perspective. Trolox equivalent antioxidant capacity (TEAC) of six vegetal aqueous extracts (Symphitum officinalae (radix)- SYM, Inula helenium (radix)- INU, Calendula officinalis (flores)- CAL, Angelica arhanghelica (folium)-ANG( F), Angelica arhanghelica (radix)- ANG(R), Ecbalium Elaterium (fruits)- ECB) and luminol-enhanced chemiluminescence of PMNL on addition of these vegetal extracts were measured. Percentages from the maximal or minimal values obtained were calculated for each extract (TEAC%, PMNL stimulation%, PMNL inhibition%, relative speed of action% (RSA%%)), specific Yin-Yang significance was assigned to each relative parameter. In the end, an integration of all the relative values was done, in order to find a global "Yin" or a "Yang" trait of each vegetal extract.
Results: TEAC decreased in the following order: SYM > INU > CAL > ANG(F) > ANG(R > ECB. Three vegetal extracts (SYM > INU > ECB) decreased the luminol- enhanced chemiluminescence of PMNL, two (ANG(R) > ANG(F)) increased it, while one (CAL) had a dual effect. After the integration of the percentages, CAL was found to have a global "Yang" trait, while the rest of the plants had a global "Yin" trait.
Conclusions: TEAC% and PMNL inhibition% appears to correlate with the Yin properties of herbs, while PMNL stimulation% and RSA% might correlate with Yang aspects within the formal TCM classification system, and may be useful criteria in describing the Western herbs from a TCM point of view.
... [25] The other publications focus on Cordyceps, examining: pharmacological functions and development of products; [3] production, isolation, purification, structure elucidation, and pharmacological action of polysaccharide; [1] chemical constituents; [26] preparations and chemical structures of polysaccharide; [27] taxonomic concepts, preparations, apoptosis, chemical constituent profiling, hosts, and poisoning; [28] history, medicinal uses, chemical composition, and cultivation; [29] pharmacological actions; [30] and the pharmacological basis of " Yin-nourishing (養陰 Yǎng Yīn) " and " Yang-invigorating (壯陽 Zhuàng Yáng) " actions. [31] TERMINOLOGY OF " DONGCHONGXIACAO " WITH REGARD TO CORDYCEPS " DongChongXiaCao " is commonly known as " yarsa gumba " in Tibetan, because " yarsa " means winter and " gumba " means summer. " Gunba " or " gonba " has also been used to replace " gumba, " and the fungus is named " keera jhar " (insect herb) in the Indian mountains. ...
The caterpillar fungus Ophiocordyceps sinensis (syn.†
Cordyceps sinensis), which was originally used in traditional Tibetan and Chinese medicine, is called either “yartsa gunbu” or “DongChongXiaCao (冬蟲夏草 Dōng Chóng Xià Cǎo)” (“winter worm-summer grass”), respectively. The extremely high price of DongChongXiaCao, approximately USD $20,000 to 40,000 per kg, has led to it being regarded as “soft gold” in China. The multi-fungi hypothesis has been proposed for DongChongXiaCao; however, Hirsutella sinensis is the anamorph of O. sinensis. In Chinese, the meaning of “DongChongXiaCao” is different for O. sinensis, Cordyceps spp.,‡ and Cordyceps spƒ. Over 30 bioactivities, such as immunomodulatory, antitumor, anti-inflammatory, and antioxidant activities, have been reported for wild DongChongXiaCao and for the mycelia and culture supernatants of O. sinensis. These bioactivities derive from over 20 bioactive ingredients, mainly extracellular polysaccharides, intracellular polysaccharides, cordycepin, adenosine, mannitol, and sterols. Other bioactive components have been found as well, including two peptides (cordymin and myriocin), melanin, lovastatin, γ-aminobutyric acid, and cordysinins. Recently, the bioactivities of O. sinensis were described, and they include antiarteriosclerosis, antidepression, and antiosteoporosis activities, photoprotection, prevention and treatment of bowel injury, promotion of endurance capacity, and learning-memory improvement. H. sinensis has the ability to accelerate leukocyte recovery, stimulate lymphocyte proliferation, antidiabetes, and improve kidney injury. Starting January 1st, 2013, regulation will dictate that one fungus can only have one name, which will end the system of using separate names for anamorphs. The anamorph name “H. sinensis” has changed by the International Code of Nomenclature for algae, fungi, and plants to O. sinensis.
... Recent literature further confirms that Cordyceps enhances cellular energy in the form of ATP (adenosine tri-phosphate). Upon hydrolysis of phosphates from ATP, lots of energy is released which is further used by the cell (Dai et al. 2001;Siu et al. 2004). The studies by many researchers in the past on Cordyceps have demonstrated that it has anti-bacterial, anti-fungal, larvicidal, anti-inflammatory, anti-diabetic, anti-oxidant, anti-tumor, pro-sexual, apoptotic, immunomodulatory, anti-HIV and many more activities (Table 2). ...
An entomopathogenic fungus, Cordyceps sp. has been known to have numerous pharmacological and therapeutic implications, especially, in terms of human health making it a suitable candidate for ethno-pharmacological use. Main constituent of the extract derived from this fungus comprises a novel bio-metabolite called as Cordycepin (3′deoxyadenosine) which has a very potent anti-cancer, anti-oxidant and anti-inflammatory activities. The current review discusses about the broad spectrum potential of Cordycepin including biological and pharmacological actions in immunological, hepatic, renal, cardiovascular systems as well as an anti-cancer agent. The article also reviews the current efforts to delineate the mechanism of action of Cordycepin in various bio-molecular processes. The study will certainly draw the attention of scientific community to improve the bioactivity and production of Cordycepin for its commercial use in pharmacological and medical fields.
... Numerous pharmacological effects of CS have been reported such as anti-tumor [4,5], immunomodulatory678, anti-inflammatory91011, and anti-oxidant properties [12,13] . Furthermore, CS possesses both suppressive and enhancive properties with regard to human immunity, which could be a reference to the Yin-Yang characteristics of CS described in traditional Chinese medicine [14]. Several reports have evinced this dual modality from the immunological and pharmacological perspective [7,151617. ...
Cordyceps sinensis (CS) has been commonly used as herbal medicine and a health supplement in China for over two thousand years. Although previous studies have demonstrated that CS has benefits in immunoregulation and anti-inflammation, the precise mechanism by which CS affects immunomodulation is still unclear. In this study, we exploited duplicate sets of loop-design microarray experiments to examine two different batches of CS and analyze the effects of CS on dendritic cells (DCs), in different physiology stages: naïve stage and inflammatory stage. Immature DCs were treated with CS, lipopolysaccharide (LPS), or LPS plus CS (LPS/CS) for two days, and the gene expression profiles were examined using cDNA microarrays. The results of two loop-design microarray experiments showed good intersection rates. The expression level of common genes found in both loop-design microarray experiments was consistent, and the correlation coefficients (Rs), were higher than 0.96. Through intersection analysis of microarray results, we identified 295 intersecting significantly differentially expressed (SDE) genes of the three different treatments (CS, LPS, and LPS/CS), which participated mainly in the adjustment of immune response and the regulation of cell proliferation and death. Genes regulated uniquely by CS treatment were significantly involved in the regulation of focal adhesion pathway, ECM-receptor interaction pathway, and hematopoietic cell lineage pathway. Unique LPS regulated genes were significantly involved in the regulation of Toll-like receptor signaling pathway, systemic lupus erythematosus pathway, and complement and coagulation cascades pathway. Unique LPS/CS regulated genes were significantly involved in the regulation of oxidative phosphorylation pathway. These results could provide useful information in further study of the pharmacological mechanisms of CS. This study also demonstrates that with a rigorous experimental design, the biological effects of a complex compound can be reliably studied by a complex system like cDNA microarray.
... Sacc., which consists of the fruiting body (CsA) and the host caterpillar (CsB), has long been used in China as a food or herbal medicine to treat numerous diseases (Bok, Lermer, Chilton, Klingeman, & Towers, 1999). Pharmacological studies have shown that C. sinensis possesses wide biological activities including anti-oxidation, immuno-potentiation, antitumorigenesis, antiinflammation, and stimulation of testosterone biosynthesis (Bok et al., 1999;Buenz, Bauer, Osmundsonc, & Motley, 2005;Chen, Huang, & Huang, 2005;Li, Li, Dong, & Tsim, 2001;Lo, Tu, Lin, & Lin, 2004;Siu et al., 2004;Weng, Chou, Lin, Tsai, & Kuo, 2002;Yu, Wang, Huang, & Duh, 2006). ...
The caterpillar-shaped Chinese medicinal mushroom Cordyceps sinensis consists of the fruiting body (CsA) and the host caterpillar (CsB). Ergosterol is a principal sterol in fungi and can indicate the level of mycelia of C. sinensis. Ergosterol is present in two forms, as free ergosterol and esterified ergosterol, which have different physiological functions. The relative abundances of free to esterified ergosterol are different among the various species. In the present study, a gradient reversed-phase high-performance liquid chromatography (HPLC) method was developed for the simultaneous determination of free and esterified ergosterol in CsA and CsB of C. sinensis. The results showed that CsA and CsB had similar ergosterol compositions, but the level of ergosteryl esters in CsB was much higher than that in CsA, indicating that CsA and CsB might be in different growth phase or have different physiological functions for the growth and multiplication of C. sinensis.
... Given that many antioxidants are immunomodulating. The herb Cordyceps (Cordyceps sinensis) enhanced the concanavalin A (Con A)-stimulated splenocytes proliferation and the myocardial ATP generation capacity, which were disseminated in terms of TCM as 'yinnourishment' and 'yang-invigoration', respectively (Siu et al., 2004). This is consistent with the notion of Ko and Leung (Ko & Leung, 2007) that yin-herbs, in addition to their significant antioxidant capcities, also possess immunomodulatory properties, including mitogen-stimulated proliferation of mouse splenocytes, cytokines secretion, leukocyte migration, and antibody production. ...
... Indeed, different therapeutic purposes of C.CS-4 have been reported (Zhu et al., 1998a;1998b;Buenz et al., 2005). Interestingly, it has immuno-modulating and immuno-regulating activities, and is widely used in supporting renal health and respiratory health (Zhou et al., 2009;Siu et al., 2004). In some clinical research, C.CS-4 has been used as an additional immunosuppressant in preventing acute rejection in organ transplantation (Li et al., 2009b). ...
Cordyceps CS-4 (C.CS-4), a vegetative form of Cordyceps that contains the same active compounds as the fruit body, is widely used as a substitute of Cordyceps in China. A number of studies have shown that Cordyceps can positively stimulate the activation of T lymphocytes, B lymphocytes, natural killer cells, and macrophages. In our previous study, we found that C.CS-4 could inhibit the proliferation of CD4+ T cells in autoimmune diseases and prevent the lymphocyte infiltration in tissues. However, it is still unclear how the lymphocytes are regulated by C.CS-4. In this study, we investigate the effect of C.CS-4 on human monocyte-derived dendritic cells (Mo-DCs), which are generated from PBMCs by the treatment with GM-CSF and IL-4. It is observed that Mo-DCs pretreated with C.CS-4 show an immature phenotype. Moreover, C.CS-4 significantly inhibits proliferation of CD4+ T cells, attenuates the production of cytokines in Mo-DCs and balances the Th1 and Th2 response in immune system. Our findings indicate that C.CS-4 exerts the immunosuppressive effect through inhibiting the CD4+ T cells proliferation, regulating cytokine secretions of Th1 and Th2 response (Mo-DCs) and inducing phenotypic immature of Mo-DCs which may be related to the antigen presenting dysfunction.
... Manabe et al (1996Manabe et al ( , 2000 found that C. sinensis mycelial extract (200 mg kg À1 daily orally) increases hepatic energy metabolism, as demonstrated by liver ATP:Pi value, in diet-induced hypoferric anaemic mice by increasing hepatic blood flow. C. sinensis stimulates mitochondrial electron transport and ATP production (Siu et al 2004). Dai et al (2001) found that CordyMax Cs-4 improves the bioenergy status in the mouse liver. ...
Cordyceps species, including C. sinensis, C. militaris, C. pruinosa and C. ophioglossoides, are prized traditional medicinal materials. The aim of this article is to review the chemical constituents and pharmacological actions of Cordyceps species. The chemical constituents include cordycepin (3'-de-oxyadenosine) and its derivatives, ergosterol, polysaccharides, a glycoprotein and peptides containing alpha-aminoisobutyric acid. They include anti-tumour, anti-metastatic, immunomodulatory, antioxidant, anti-inflammatory, insecticidal, antimicrobial, hypolipidaemic, hypoglycaemic, anti-ageing, neuroprotective and renoprotective effects. Polysaccharide accounts for the anti-inflammatory, antioxidant, anti-tumour, anti-metastatic, immunomodulatory, hypoglycaemic, steroidogenic and hypolipidaemic effects. Cordycepin contributes to the anti-tumour, insecticidal and antibacterial activity. Ergosterol exhibits anti-tumour and immunomodulatory activity. A DNase has been characterized.
... Pharmacological studies have shown that Cordyceps possesses a wide spectrum of biological activities including antioxidation61626364, immunopotentiation65666768, anti-tumorigenesis68697071, anti-inflammation Retarding the aging process [72] and stimulation of testosterone biosynthesis [73]. We have recently investigated the effects of wild and cultured Cordyceps on Con A-stimulated splenocytes (an in vitro bioassay for Yin tonifying action) and myocardial ATP generation capacity (an ex vivo bioassay for Yang tonifying action) [74]. The results indicated that methanolic extracts of wild and cultured Cordyceps enhanced both the Con A-stimulated splenocyte proliferation in vitro and myocardial mitochondrial ATP generation ex vivo in mice, with no significant difference in potencies when the two types of Cordyceps were compared. ...
Chinese tonifying herbs such as herba cistanche, ganoderma and cordyceps, which possess antioxidant and/or immunomodulatory activities, can be useful in the prevention and treatment of age-related diseases. Pharmacological studies on Yang and Yin tonifying herbs suggest that Yang tonifying herbs stimulate mitochondrial adenosine triphosphate (ATP) generation, presumably through the intermediacy of reactive oxidant species, leading to the enhancement of cellular/mitochondrial antioxidant status. Yin tonifying herbs, however, apart from possessing antioxidant properties, exert mainly immunomodulatory functions that may boost a weak immune system and may also suppress overreactive immune responses. The abilities of Yang and Yin Chinese tonifying herbs to enhance ATP generation and to exhibit antioxidant and/or immunomodulatory actions are the pharmacological basis for their beneficial effects on the retardation of aging.
Ethnopharmacological relevance: Cordyceps has a long medicinal history as a nourishing herb in traditional Chinese medicine (TCM). Ischemic cardio-cerebrovascular diseases (CCVDs), including cerebral ischemic/reperfusion injury (CI/RI) and myocardial ischemic/reperfusion injury (MI/RI), are major contributors to mortality and disability in humans. Numerous studies have indicated that Cordyceps or its artificial substitutes have significant bioactivity on ischemic CCVDs, however, there is a lack of relevant reviews.
Aim of the study: This review was conducted to investigate the chemical elements, pharmacological effects, clinical application and drug safety of Cordycepson ischemic CCVDs.
Materials and methods: A comprehensive search was conducted on the Web of Science, PubMed, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases using the keywords "Cordyceps", "Cerebral ischemic/reperfusion injury", and "Myocardial ischemic/reperfusion injury" or their synonyms. The retrieved literature was then categorized and summarized.
Results: The study findings indicated that Cordyceps and its bioactive components, including adenosine, cordycepin, mannitol, polysaccharide, and protein, have the potential to protect against CI/RI and MI/RI by improving blood perfusion, mitigating damage from reactive oxygen species, suppressing inflammation, preventing cellular apoptosis, and promoting tissue regeneration. Individually, Cordyceps could reduce neuronal excitatory toxicity and blood-brain barrier damage caused by cerebral ischemia. It can also significantly improve cardiac energy metabolism disorders and inhibit calcium overload caused by myocardial ischemia. Additionally, Cordyceps exerts a significant preventive or curative influence on the factors responsible for heart/brain ischemia, including hypertension, thrombosis, atherosclerosis, and arrhythmia.
Conclusion: This study demonstrates Cordyceps' prospective efficacy and safety in the prevention or treatment of CI/RI and MI/RI, providing novel insights for managing ischemic CCVDs.
Keywords: Cardio-cerebrovascular diseases; Cerebral ischemic/reperfusion injury; Chemical components; Chinese Cordyceps; Myocardial ischemic/reperfusion injury; Pharmacological activities.
Background:
Low quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) receiving adjuvant chemotherapy after radical resection is a major global health issue. High-quality evidence for the effectiveness of Shenlingcao oral liquid (SOL) as a complementary treatment in this patients is lacking at present.
Purpose:
To determine whether complementary SOL treatment in NSCLC patients receiving adjuvant chemotherapy would yield greater improvements in QoL than chemotherapy alone.
Study design:
We conducted a multicenter, randomized controlled trial of stages IIA-IIIA NSCLC patients undergoing adjuvant chemotherapy in seven hospitals.
Methods:
Using stratified blocks, participants were randomized in a 1:1 ratio to receive SOL combined with conventional chemotherapy or conventional chemotherapy alone. The primary outcome was the change in global QoL from baseline to the fourth chemotherapy cycle, and intention-to-treat analysis was applied with a mixed-effect model. Secondary outcomes were functional QoL, symptoms, and performance status scores at the 6-month follow-up. Missing data were handled with multiple imputation and a pattern-mixture model.
Results:
Among 516 randomized patients, 446 (86.43%) completed the study. After the fourth chemotherapy cycle, in comparison with the control group, patients receiving SOL showed a lower reduction in mean global QoL (-2.76 vs. -14.11; mean difference [MD], 11.34; 95% confidence interval [CI], 8.28 to 14.41), greater improvement in physical function (MD, 11.61; 95% CI, 8.57 to 14.65), role function (MD, 10.15; 95% CI, 5.75 to 14.54), and emotional function (MD, 4.71; 95% CI, 1.85 to 7.57), and greater improvements in lung cancer-related symptoms (e.g., fatigue, nausea/vomiting, and appetite loss) and performance status during the 6-month follow-up period (treatment main effect, p < 0.05).
Conclusion:
SOL treatment for NSCLC patients receiving adjuvant chemotherapy can significantly improve QoL and performance status within 6 months after radical resection.
Trial registration:
ClinicalTrials.gov identifier: NCT03712969.
Purpose of Review
In the present review, two strain improvement strategies viz. transformation system development and inter-specific protoplast fusion for this mushroom are hypothesized.
Recent Findings
The entomopathogenic medicinal mushroom Cordyceps species has been bestowing health biologically and pharmacologically for years. It harbors a variety of bio-metabolites having far-ranging activities. One of the constituents, cordycepin alone, is involved in a plethora of biochemical and molecular processes. With this interest, the bottlenecks such as excessive harvesting, commercial cultivation, low frequency of artificial stromata formation are still on pace. The genus Cordyceps has characteristic genomic expansion and studies such as identification of mating-type genes, metabolite-producing genes, and strain improvement techniques are in great demand.
Summary
In order to understand the present demand and current scenario regarding the genus Cordyceps, efforts have been made to elucidate the significance of its major bioactive constituent and underlying wide-spectrum applications. Furthermore, through this review, one may understand the situation and demand of mushroom in the present world. Furthermore, this article would certainly help to maneuver this fungus for developing drugs against dreadful human diseases.
This study aimed to investigate the effect of Cordyceps militaris extract on the proliferation and apoptosis of carboplatin- resistant SKOV-3 and determine the underlying mechanisms for overcoming carboplatin resistance in human ovarian cancer. We cultured the carboplatin-resistant SKOV-3 cells in vitro until the exponential growth phase and then treated with different concentrations of C. militaris for 24, 48, and 72 hours. We performed cell proliferation assay, cell morphological change assessment using transmission electron microscopy, apoptosis assay, and immunoblotting to measure the protein expression of caspase-3 and -8, poly (ADP-ribose) polymerase (PARP)-1, B-cell lymphoma (Bcl)-2, and activating transcription factor 3 (ATF3)/TP53 signaling-related proteins. As a result, C. militaris reduced the viability of carboplatin-resistant SKOV-3 and induced morphological disruptions in a dose- and time-dependent manner. The gene expression profiles indicated a reprogramming pattern of the previously known and unknown genes and transcription factors associated with the action of TCTN3 on carboplatin-resistant SKOV-3 cells. We also confirmed the C. militaris-induced activation of the ATF3/TP53 pathway. Immunoblotting indicated that cotreatment of C. militaris and carboplatin-mediated ATF3/TP53 upregulation induced apoptosis in the carboplatin-resistant SKOV-3 cells, which are involved in the serial activation of pro-apoptotic proteins, including Bcl-2, Bax, caspases, and PARP-1. Further, when the ATF3 and TP53 expression increased, the CHOP and PUMA expressions were upregulated. Consequently, the upregulated CHOP/PUMA expression activated the positive regulation of the apoptotic signaling pathway. In addition, it decreased the Bcl-2 expression, leading to marked ovarian cancer cells sensitive to carboplatin by enhancing apoptosis. We then corroborated these results using in vivo experiments. Taken together, C. militaris inhibits carboplatin-resistant SKOV-3 cell proliferation and induces apoptosis possibly through ATF3/TP53 signaling upregulation and CHOP/PUMA activation. Therefore, our findings provide new insights into the treatment of carboplatin-resistant ovarian cancer using C. militaris.
Cordyceps, one of the most valued traditional Chinese medicines, consists of the dried fungus Cordyceps sinensis growing on the larva of caterpillar. It is also known as 'winter-worm and summer-grass' because of its appearance during different seasons. The parasitic complex of the fungus and the caterpillar is found in soil of a prairie at an elevation of 3,500 to 5,000 meters in northwestern part of China. According to Chinese medicinal theory, Cordyceps is used to replenish the kidney and soothe the lung, and indeed many clinical applications have been reported. The natural Cordyceps is rare and expensive on the local market, and therefore, several mycelial strains have been isolated from natural Cordyceps and manufactured in large quantities by fermentation technology, and they are commonly sold as health food products in Orient. The adulterants of Cordyceps are commonly found on the market, and therefore the authentication of these products has to be defined. Having the urgent need from current market, different chemical markers such as nucleoside, ergosterol, mannitol and polysaccharide are being used for quality control of Cordyceps. Unfortunately, these markers are far from optimization, and therefore extensive works are needed to define the pharmacological efficiency of these markers.
It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Administration of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.
Objective: To screen high-producing Cordyceps militaris strain and increase the yield of mycelium and content of active component in mycelium during fermentation of C. militaris strain. Methods: The mutation of C. militaris CGMCC5.699 strain was induced with nitrosoguanidine (NTG), based on which the high producing strain was preliminarily screened according to the growth rate of mycelium and the sizes of colonies, and further screened by culture in shake-flask according to the dry weight as well as adenosine, polysaccharide, protein and mannitol contents of mycelium, then subcultured continuously to evaluate the genetic stability. Results: Thirty-three mutant strains with high dry weight of mycelium as well as high adenosine, polysaccharide, protein and mannitol contents were obtained, of which 8 strains showed stable genetic mutation characters. The dry weight as well adenosine, polysaccharide, protein and mannitol contents of H4025 strain increased by 103%, 545%, 43.5%, 51.9% and 42.7% as compared with those of CGMCC5.699 strain respectively. Conclusion: A high-producing C. militaris mutant H4025 strain was successfully screened.
Cordyceps sinensis is a valuable Chinese traditional medicine, which has antitumour activity, immunopo-tentiation, hypocholesterolemic effect, hypoglycemic activity and antioxidant properties, etc. The adlay was used as a medium for both C. sinensis submerged and solid-state fermentation, and the fermentative products were analyzed for antioxidant component (crude polysaccharide, total phenol and flavonoids) and antioxidant activities (scavenging DPPH free radicals ability, ferrous ion-chelating ability and reducing power). The hot water extract and crude polysaccharide from fermentative on immunomodulatory effects were evaluated. The water extract of C. sinensis submerged fermentative adlay product had higher antioxidant components such as crude polysaccharide, total phenol and flavonoids than un-fermentative product. Solid-state fermentative adlay product had higher antioxidant components such as polysaccharide and flavonoid than unfermentative adlay. The water extract of C. sinensis submerged fermentative adlay products had higher antioxidant properties such as scavenging DPPH free radicals and reducing power than unfermentative adlay. Solid-state fermentative adlay products had higher scavenging DPPH free radicals ability and reducing power than unfermentative adlay. Both hot water extracts and crude polysaccharides from C. sinensis submerged and solid-state fermentative adlay products increased the proliferation rate of macrophage. Both 5 μg/mL hot water extracts and crude polysaccharides from C. sinensis fermentative adlay products significantly down-regulated iNOS mRNA expression.
In order to determine the functional benefits of Cordyceps militaris in the immune system, we examined the immunomodulatory activities of Cordyceps militaris in an immunocompromised C57BL/6 mice model. Mice were injected intraperitoneally with an immunosuppressive drug, cyclophosphamide, and then administered orally with 3% hydroxypropylmethylcellulose or 30, 100, and 300 mg/kg of 50% ethanol extract of Cordyceps militaris (CM 30, CM 100, and CM 300, respectively) for 12 days. Mice treated with CM displayed significantly increased splenocyte proliferation and natural killer cell activity compared to immunosuppressed control mice (p<0.05). The spleen cells isolated from mice treated with CM also displayed increased production of Th1 cytokines, including IL-2, IL-12, IFN-γ and TNF-α, suggesting enhanced cellular immunity in response to CM. However, CM had no significant effect on the production of IL-4 and IL-10. These results indicate that Cordyceps militaris enhances immune function by promoting immune cell proliferation and Th1 cytokine production.
The Route of Cordyceps
Ophiocordyceps sinensis, also called cordyceps, belongs to traditional Chinese and Tibetan pharmacopoeias. This medicinal fungus native to the high Himalayan mountains is used as a tonic and an aphrodisiac. As it spread all over the world, its production processes, pharmaceutical forms and indications have multiplied. From Aids to cancer and diabetes, it has become a true panacea for the pharmacopeia of alternative and complementary medicines. Locally, cordyceps has become the main business in an economy that reshapes the Tibetan society. An outline of the biography of cordycepsis proposed through a multilocation anthropological approach. This biography includes material and symbolic features and specifically examines the validation process that combines “traditional” and “modern” allegations, references to nature, and scientific validation.
Processing technologies, which are required in the production of traditional Chinese medicine (TCM), has garnered attention in recent years. To address challenges associated with processed TCM and to promote its development in academia and industries, the application of metabolomics was introduced in this review, which primarily focuses on exploring TCM theories, identification of discovered compounds, and the evaluation and quality control of TCM through metabolomics. Thus metabolomics could be a powerful method for the TCM processing industry.
Traditional Chinese medicinal herbs have been used for thousands of years to treat numerous ailments. In recent years, these herbs have been the focus of attention due to their medicinal and pharmacological benefits. In the present study, 25 types of herbs commonly used in Chinese medicinal culinary diets were quantitatively investigated for their various antioxidant activities. Using the 1,1-diphenyl-2-picrylhydrazyl high pressure liquid chromatography and 2-deoxyguanosine oxidation methods, the highest antioxidant activity was found in chrysanthemum (Ju Hua), followed by hawthorn (Shan Zha), licorice root (Gan Cao), hibiscus (Luo Shen Hua), cassia seed (Jue Ming Zi) and Chinese wolfberry (Gou Gi), while poria (Fu Ling) and adlay (Yi Yi Ren) contained the lowest antioxidant activity. The same trend was also observed for total phenolic content using the Folin-Ciocalteu method. Ascorbic acid and tocopherol were only detected in trace amounts, suggesting that phenolic compounds may be the main contributors to herbal antioxidant activities.
Complex of Paecilomyces sinclairii and host larvae, Bombyx mori, is a well known health food; however, concerns about nephrotoxicity have been raised. Kidney toxicity was investigated after 13 weeks of administering the complex orally to rats with parameters including blood urea nitrogen (BUN), creatinine, and kidney damage biomarkers, beta-2-microglobulin (β2m), glutathione S-transferase alpha (GST-α), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin. Dose-dependent kidney cell karyomegaly and tubular hypertrophy were observed, with higher severity in males. There was a dose-dependent increase in KIM-1 and TIMP-1 levels in kidney and urinary KIM-1, cystatin C, β2m, and osteopontin levels. KIM-1 and TIMP-1 increased in male kidneys had not recovered by 2 weeks after stopping exposure. Cystatin C in kidney was significantly lowered in all treatment groups at 13 weeks of administration. All the changes were more noticeable in males. These data indicate that the complex damage renal tubule cells with histopathological lesions and changes in biomarker levels. Kidney and urinary KIM-1 and cystatin C were the most markedly affected and early increased indicators among biomarkers tested, whereas BUN and creatinine were not affected.
Mycelia of cultured Cordyceps sinensis (CS) is one of the most common substitutes for natural CS and was approved for arrhythmia in China. However, the role of CS in ameliorating injury during ischemia-reperfusion (I/R) is still unclear. We examined effects of extracts from CS on I/R and investigated the possible mechanisms. Post-ischemic coronary perfusion pressure, ventricular function, and coronary flow were measured using the Langendorff mouse heart model. Oxidative stress of cardiac homogenates was performed using an ELISA. Our results indicate that CS affords cardioprotection possibly through enhanced adenosine receptor activation. Cardioprotection was demonstrated by reduced post-ischemic diastolic dysfunction and improved recovery of pressure development and coronary flow. Treatment with CS largely abrogates oxidative stress and damage in glucose- or pyruvate-perfused hearts. Importantly, observed reductions in oxidative stress [glutathione disulfide (GSSG)]/[GSSG + glutathione] and [malondialdehyde (MDA)]/[superoxide dismutase + MDA] ratios as well as the resultant damage upon CS treatment correlate with functional markers of post-ischemic myocardial outcome. These effects of CS were partially blocked by 8-ρ-sulfophenyltheophylline, an adenosine receptor antagonist. Our results demonstrate a suppressive role of CS in ischemic contracture. Meanwhile, the results also suggest pre-ischemic adenosine receptor activation may be involved in reducing contracture in hearts pretreated with CS. Copyright © 2012 John Wiley & Sons, Ltd.
Cordyceps sinensis has been used as a precious herbal medicine for thousands of years in China. Its polysaccharide fraction has been confirmed possessing immunomodulatory function and we have reported the acid polysaccharide fraction (APSF), from an anamorph of C. sinensis, has stimulating activity on macrophages. The mechanism still needs to be further elucidated.
In order to investigate the effects of APSF on macrophage's phenotypes, Ana-1 mouse macrophages were polarized to M2 phenotype by culturing the cells with culture supernatant of H22 cells. M2 phenotype was determined by measuring the expression of TNF-α and checking cell surface markers mannose receptor (MR) and scavenger receptor (SR). After cultured with H22 supernatant for 72 h, the TNF-α level of Ana-1 cells was decreased while the SR and MR expressions were up-regulated, suggesting that Ana-1 cells were polarized towards M2 macrophages. Then the effects of APSF on M2 macrophages were investigated by measuring mRNA levels of TNF-α, inducible nitric oxide synthase (iNOS), IL-12 and IL-10. Nuclear NF-κB was detected by Western blotting.
APSF treatment increased the expressions of TNF-α, IL-12 and iNOS, and reduced the expression of IL-10 of Ana-1 cells. Besides, the expressions of SR and MR were down-regulated by APSF. And the result of Western blotting showed NF-κB level was decreased in M2 macrophages and up-regulated after APSF treatment.
APSF may convert M2 macrophages to M1 phenotype by activating NF-κB pathway.
Due to the rarity and outstanding curative effects of C. sinensis, some natural substitutes such as C. militaris, C. liangshanensis, C. gunnii, and C. cicadicola have been sold in markets (Yang et al. 2009). In addition, several cultured mycelia of C. sinensis and C. militaris fungi have become the main substitutes of the natural species as commercial products, and 50 medicines and two dietary supplements related to cultured Cordyceps have been approved by the State Food and Drug Administration of China since 2002 (Feng, Yang, and Li 2008). For example, JinShuiBao capsule, the commercial product of Cs-4 (Paecilomyces hepialid, a standardized mycelium of C. sinensis), has been used in clinics throughout China. This product generates several million U.S. dollars every year. Synnematum sinensis, Cephalosporium sinensis, Gliocladium roseum, and Mortierella hepialid, the fungus strains isolated from natural C. sinensis, have also been subjected to large- scale fermentation and are used as commercial products (Cheung, Li, and Tsim 2005). Therefore, much effort has been invested in studying the evaluation of the quality, pharmacological activities, and clinical efficacies of natural and cultured cordyceps. In this chapter, we focus on the bioactivities, action mechanisms, and active ingredients of cordyceps, both natural and cultured.
The present study was designed to investigate the molecular weight (MW), chemical composition and effect of polysaccharide (CS-PS), from the fruiting bodies of cultured Cordyceps sinensis, on immune function and anti-oxidation activity of BALB/c mice exposed to (60)Co.
The MW of CS-PS was determined by gel-filtration. The chemical composition of CS-PS was tested by using gas chromatography-mass spectrophotometer (GC-MS). Mice were administered CS-PS with doses of 50, 100 or 200mg/kg body weight, then exposed to (60)Co. The normal control group and irradiated control group were also used. Four days later, lymphocyte proliferation, activity of macrophage phagocytosis, delayed type hypersensitivity (DTH), concentration of malondialdehyde (MDA), total-superoxide dismutase (SOD) enzyme activity, and cytokine expression in serum from the mice were tested.
The average molecular weight of CP-PS was 12 kD. The polysaccharide was composed of mannose, rhamnose, arabinose, xylose, glucose and galactose. Lymphocyte proliferation, the activity of macrophage phagocytosis, DTH and total-SOD enzyme activity in the CS-PS groups were significantly enhanced compared to the irradiated control group. Lipid peroxidation level was significantly reduced in the CS-PS groups compared to the irradiated control group. Levels of cytokine IL-4, IL-5 and IL-17 are also affected in the CS-PS groups compared to the irradiated control group.
CS-PS, a heteropolysaccharide, enhances immunity activity in mice treated by ionizing radiation, through reducing oxidative injury and modulating the secretion of cytokine IL-4, IL-5 and IL-17.
This study is to investigate the effect of Cordyceps sinensis and its cultured mycelia on growth and metabolism of Escherichia coli, and microcalorimetric method was carried out to evaluate its biological activity. The study will provide the basis for the quality control of Cordyceps sinensis. Experimental result will show the effect of natural Cordyceps sinensis and its cultured mycelia on growth and metabolism of Escherichia coli, with index of P(1max) and effective rate (E) by microcalorimetry, the data of experiment were studied by cluster analysis. The results showed that Cordyceps sinensis and its cultured mycelia not only can promote growth and metabolism of Escherichia coli but also can regulate the balance of intestinal microecology efficiently. When the concentrations of samples > 6.0 mg mL(-1), natural Cordyceps sinensis can promote the growth and metabolism of Escherichia coli efficiently (P < 0.05) compared with the control group, and have better dose-effect relationship with concentration (r > 0.9), its cultured mycelia does not show conspicuous auxoaction (P > 0.05) and have not dose-effect relationship with concentration (r < 0.6); when the concentration of samples < 6.0 mg mL(-1), all samples does not show conspicuous auxoaction (P > 0.05). Natural Cordyceps sinensis and its cultured mycelia can be distinguished by cluster analysis. Microcalorimetry has a good prospect on the quality evaluation of the traditional Chinese medicine.
Cordyceps sinensis (CS) is a parasitic fungus, and it has been used widely in traditional Chinese medicines (TCM) for centuries. Many studies have shown that CS has immunoregulatory activity in many disease models, but the underlying mechanism remains elusive. We studied whether CS could suppress the onset of diabetes by altering T lymphocyte subsets in non-obese diabetic (NOD) mice. We found that the onset of type 1 diabetes in NOD mice was associated with an imbalance of CD4(+)CD25(+)FoxP3(+) regulatory T (Treg) cells and IL-17 producing Th17 cells. Oral administration of CS resulted in reduction in the overall incidence of diabetes, and this was due to an increase in the ratio of Treg cells to Th17 in the spleen and pancreatic lymph nodes (PLNs). Taken together, these data imply that CS is able to modulate Treg to Th17 cell ratio in vivo, thus contributing to the inhibition of diabetes.
The commercially available HERBSnSENSEStrade mark Cordyceps (HSCS) belongs to a cultivated strain of Cordyceps sinensis whose immunomodulatory activities has been renowned in traditional Chinese medicine (TCM) for centuries. The present report is the first that describes its immunomodulatory features through a series of in vitro and in vivo experiments. We measured, in peripheral blood mononuclear cells the in vitro effects of HSCS on the gene expression of cytokines and cytokine receptors, cytokine release, and surface expression of cytokine receptors using cDNA expression array, cytometric bead array (CBA), and immunoflorescence staining, respectively, as well as macrophage phagocytosis and monocyte production of H2O2 using flow cytometry. Sixty female BALB/c mice were fed with either HSCS (40 mg/kg/day) or water consecutively for 14 days. Proliferation, cytokine liberation, and CD3/4/8 expression of splenic cells were measured using 5-bromo-2'-deoxyuridine proliferation ELISA, CBA, and cytometry immunoflorescence staining, respectively. In vitro results demonstrated that HSCS induced the production of interleukin(IL)-1beta, IL-6, IL-10 and tumor necrosis factor alphaalpha from PBMC, augmented surface expression of CD25 on lymphocytes, and elevated macrophage phagocytosis and monocyte production of H2O2. In vivo results showed that HSCS did not induce splenomegaly and cytokine overliberation. Our results possibly provide the biochemical basis for future clinical trials.
Traditional Chinese medicine (TCM) has been widely practiced and is considered as an attractive to conventional medicine. Multi-herb recipes have been routinely used in TCM. These have been formulated by using TCM-defined herbal properties (TCM-HPs), the scientific basis of which is unclear. The usefulness of TCM-HPs was evaluated by analyzing the distribution pattern of TCM-HPs of the constituent herbs in 1161 classical TCM prescriptions, which shows patterns of multi-herb correlation. Two artificial intelligence (AI) methods were used to examine whether TCM-HPs are capable of distinguishing TCM prescriptions from non-TCM recipes. Two AI systems were trained and tested by using 1161 TCM prescriptions, 11,202 non-TCM recipes, and two separate evaluation methods. These systems correctly classified 83.1-97.3% of the TCM prescriptions, 90.8-92.3% of the non-TCM recipes. These results suggest that TCM-HPs are capable of separating TCM prescriptions from non-TCM recipes, which are useful for formulating TCM prescriptions and consistent with the expected correlation between TCM-HPs and the physicochemical properties of herbal ingredients responsible for producing the collective pharmacological and other effects of specific TCM prescriptions.
Cordyceps sinensis is widely used as a traditional medicine for treatment of a wide variety of diseases or to maintain health. The immunomodulatory activity of polysaccharides prepared from submerged cultured C. sinensis BCRC36421 was investigated in human peripheral blood. Results demonstrated that Fr. A (exo-polysaccharides, 0.025 approximately 0.1 mg/ml) induced the production of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and IL-10 dose-dependently. Fr. A, as low as 0.025 mg/ml, could significantly augment surface expression of CD11b in monocytes and polymorphonuclear neutrophils. Functional assay revealed that Fr. A (0.05 mg/ml) also elevated phagocytosis in monocytes and PMN. On the other hand, Fr. B (intracellular polysaccharides) only moderately induced TNF-alpha release, CD11b expression, and phagocytosis at the same concentrations. Our results indicate that the immunomodulatory components of submerged cultured C. sinensis mainly reside in the culture filtrate.
Mice were given the extract of cultured Cordyceps sinensis (Cs) (200 mg/kg daily, p.o.) for 3 weeks. In vivo phosphorus-31 nuclear magnetic resonance (NMR) spectra of the liver were acquired at weekly intervals using a surface coil. From 1 to 3 weeks, a consistent increase in the ATP/inorganic phosphate ratio, which represents the high energy state, was observed in the Cs extract-treated mice. The intracellular pH of the Cs extract-treated mice was not significantly different from that of the control mice. No steatosis, necrosis, inflammation or fibrosis were observed in the liver specimens from Cs extract-treated mice.
This review presents Cordyceps sinensis (Berk.) Sacc., a fungus highly valued in China as a tonic food and herbal medicine. The extant records show the continued use of C. sinensis is now centuries old. The major chemical, pharmacological, and toxicological studies on C. sinensis and the various derived, cultured, fermented mycelial products currently in use are reviewed from the English and Chinese literature. Preclinical in vitro and in vivo studies and clinical blinded or open-label trials in to date over 2000 patients are reviewed. These studies show the main activities of the fungus in oxygen-free radical scavenging, antisenescence, endocrine, hypolipidemic, antiatherosclerotic, and sexual function-restorative activities. The safety of the fungus, its effects on the nervous system, glucose metabolism, the respiratory, hepatic, cardiovascular, and immune systems, immunologic disease, inflammatory conditions, cancer, and diseases of the kidney will be reviewed in the second part of this article to be published in the winter issue of this journal.
To evaluate effects of CordyMax Cs-4, a mycelial fermentation product of Cordyceps sinensis, on energy metabolism.
An in vivo pharmacology study using 31P nuclear magnetic resonance (NMR) spectroscopy. SUBJECTS AND STUDY INTERVENTIONS: Adult male C57-BL/6 mice were given an aqueous extract of CordyMax, 200 or 400 mg/kg per day or placebo for 7 days.
Using 31P-NMR spectroscopy to measure cellular triphosphates and inorganic phosphate, expressed as a ratio to a reference peak, and calculate tissue pH.
Steady-state beta adenosine triphosphate (ATP) increased in the liver of mice that received CordyMax (200 or 400 mg/kg per day) for 7 days, by 12.3% +/- 0.8% and 18.4% +/- 0.9%, respectively, compared to placebo controls (both p < 0.001), suggesting a higher hepatic bioenergy status in CordyMax-treated animals. Hepatic inorganic phosphate (Pi) decreased by 24.5% +/- 0.9% and 17.6% +/- 1.7% in the two treatment groups, respectively, compared to placebo controls (p < 0.001). The ratio of beta-ATP:Pi increased by 47.7% +/- 1.6% and 41.4% +/- 2.4%, respectively, in the treatment groups (both p < 0.001 compared to placebo). After discontinuation of CordyMax for 7 days, beta-ATP and Pi returned towards baseline.
CordyMax is effective in improving bioenergy status in the murine liver, suggesting a mechanism underlying the known clinical effectiveness of CordyMax in alleviating fatigue and improving physical endurance, especially in elderly subjects.
The stimulatory effect of Cordyceps sinensis (CS) on MA-10 mouse Leydig tumor cell steroidogenesis was previously demonstrated in our laboratory. In the present studies, we further determined the effect of CS on steroidogenesis in purified normal mouse Leydig cells. Different concentrations of CS (0.1-10 mg/ml) were added to Leydig cells without or with human chorionic gonadotropin (hCG) (50 ng/ml), and the steroid production was determined by radioimmunoassay (RIA). The results illustrated that CS stimulated normal mouse Leydig cell steroidogenesis in a dose-dependent relationship. CS at 3 mg/ml significantly stimulated testosterone production (p<0.05). Concerning the temporal relationship, CS at 3 mg/ml stimulated maximal testosterone production between 2 to 3 hr. Interestingly, hCG-stimulated testosterone productions were suppressed by CS in a dose-dependent relationship. CS also reduced dbcAMP-stimulated testosterone productions, which indicated that CS affected signal transduction pathway of steroidogenesis after the formation of cyclic AMP. Moreover, cycloheximide inhibited CS-treated mouse Leydig cell testosterone production, suggesting that new protein synthesis was required for CS-stimulated steroidogenesis.
In an effort to investigate the pharmacological basis for the health promoting actions of Chinese tonifying herbs in four main categories (Qi -invigorating, blood -enriching, Yin -nourishing and Yang -promoting), antioxidant and immunomodulatory activities of the methanol extracts prepared from 36 tonifying herbs were examined by both in vitro and ex vivo assay systems. The results indicated that the tested herbs showed in vitro (–40%) and ex vivo (–30%) antioxidant activities. Among the herbs, almost 60% of the Yang -promoting herbs showed in vitro antioxidant activity. The overall correlation between in vitro and ex vivo antioxidant activities was poor, except for the Yang -promoting herbs. In regard to immunomodulatory activity, the Qi -invigorating herbs (60%) and Yin -nourishing herbs (75%) showed in vitro immunostimulatory activity, whereas 56% of the Yang -promoting herbs showed in vitro immunosuppressive activity. About half (44%) of all tested herbs showed ex vivo immunostimulatory activity and 6% showed ex vivo immunosuppressive activity. The overall correlation between in vitro and ex vivo immunostimulatory activities was apparent, particularly for the Yin -nourishing and Yang -promoting herbs. The measurement of antioxidant and immunomodulatory activities may serve as a means for functionally relevant quality assessment of Chinese herbs and their related health products.
A simple binary solvent method has been developed for the simultaneous determination of creatine (Cr), phosphocreatine (PCr), ATP, ADP, AMP, GTP, GDP, IMP, NAD, inosine, adenosine, hypoxanthine and xanthine. This allows separation of the most important nucleotides present in myocardial biopsies as, for example, in studies using 31P NMR spectroscopy. In NMR spectra ATP and PCr are the only visible high-energy phosphates, therefore the status of other nucleotides and bases cannot be determined. The nucleotides, AMP degradation products, PCr and Cr in pig and rat heart muscle were resolved with 35 mM K2HPO4, 6 mM tetrabutylammonium hydrogensulfate buffer, pH 6.0, and a binary acetonitrile gradient on medium-bore, 250 mm or 125 mm x 3.9-4.6 mm I.D. steel octadecyl-bonded (C18) columns at a flow-rate of 1.5 or 1.0 ml/min. This method, optimized for use with older high-performance liquid chromatography pumps (100 microliters displacement heads), resolves the major porcine and rat myocardial nucleotides and degradation products within 22 min. The amounts found in normoxic porcine muscle are: Cr 9.21 +/- 0.75; hypoxanthine 1.40 +/- 0.14; PCr 7.20 +/- 1.2; IMP 1.34 +/- 0.13; beta NAD 1.82 +/- 0.23; AMP 0.10 +/- 0.04; GDP 0.05 +/- 0.02; ADP 1.23 +/- 0.09; GTP 0.19 +/- 0.01; ATP 4.45 +/- 0.32 mumol/g wet weight. The method, incorporating adenosine tetraphosphate as an internal standard, allows the documentation of changes in both the high-energy phosphates and their degradation products in a single analysis of myocardial samples as small as 200 micrograms (wet weight).
This paper reports the study on the effects of the ethanol extract of Cordyceps sinensis (CS-II), a potent herbal tonic, on murine and human in vitro natural killer cell (NK) activities and on murine in vivo NK activity (by 125I clearance assay), and on colony formation of B16 melanoma in mouse lungs. The results revealed that: 1. the in vivo and in vitro NK activities of mouse were both significantly augmented by intraperitoneal (ip) injection of CS-II. Besides, the inhibition of mouse NK activity by cyclophosphamide (Cy) was prevented following the administration of CS-II; 2. the in vitro NK activity of human peripheral blood mononuclear cells (PBMs) was elevated by preincubation of PBMs with CS-II; and 3. the colony formation of B16 melanoma in mouse lungs was reduced significantly by ip pretreatment of the mice with CS-II. This study indicates that CS-II may be used as an immunopotentiating agent in treating cancer and immunodeficient patients.
It was shown by flow cytometry analysis that crystalized preparation of Cordyceps sinensis (Cs-Cr) caused significant elevation of the number of T helper cells and Lyt-1/Lyt-2 (T helper to T suppressor cell) ratio both in peripheral blood and the treated mice spleen. The spleen weight, phagocyte counts and phagocytic activity were also elevated in the treated group. In addition, Cs-Cr could protect T helper cells from the immunosuppressive effects of prednisolone acetate and cyclophosphamide. These results further substantiate the fact that Cs-Cr is an immunoregulator/biological response modifier of cellular immunity and may be potentially useful in handling immunodeficient or immunosuppressed patients.
A warm water-extract (ECS) prepared from dried Cordyceps sinensis (Berk.) Sacc., a Chinese traditional medicine, was tested for antitumor activity in vivo and in vitro. Ehrlich ascites carcinoma cells (EAC), allogeneic to ICR mice and Meth A fibrosarcoma (Meth A), syngeneic to BALB/c mice were used as the target tumor cell lines. Mice were inoculated i.p. with 1 x 10(6) EAC or 1 x 10(5) Meth A on Day 0, and ECS or saline (control) was injected i.p. to the mice from Day 1 to Day 4. ECS-treatment increased the median survival time of the allogeneic mice inoculated with EAC to 316% of the control. Eight of the 10 ECS-treated mice survived on the 60th day (Day 60) after EAC implantation. ECS-treatment also increased the median survival time of the syngeneic mice inoculated with Meth A to 312% of the control. Half of the ECS-treated mice survived on Day 60. On the other hand, no cytotoxic effect of ECS was found on either EAC or Meth A in vitro. The antitumor effect of ECS seen in the allogeneic mice was significantly reduced when the mice received whole body X-irradiation (5 Gy) before EAC implantation. These results suggest that the antitumor effect of ECS may be mediated through its immunomodulating action.
The effects of protein-bound polysaccharide (SN-C) extracted from Cordyceps ophioglossoides on the growth of transplanted allogeneic and syngeneic murine tumors were studied. SN-C given by intraperitoneal administration suppressed the growth of sarcoma-180 transplanted subcutaneously in mice. Intraperitoneal administration of SN-C also caused a significant prolongation of the life span of ICR mice inoculated intraperitoneally with Ehrlich carcinoma, and C3H/He mice inoculated intraperitoneally with a syngeneic tumor (X-5563). SN-C showed a significant cytocidal effect on cultured tumor cells. SN-C did not affect delayed-type hypersensitivity (DTH) in normal mice, but restored the depressed capacity to raise DTH in tumor-bearing mice. These results suggested that SN-C may exert both direct and host-mediated antitumor effects.
Interleukin-2 (IL-2), the first of a series of lymphocytotrophic hormones to be recognized and completely characterized, is pivotal for the generation and regulation of the immune response. A T lymphocyte product, IL-2 also stimulates T cells to undergo cell cycle progression via a finite number of interactions with its specific membrane receptors. Because T cell clonal proliferation after antigen challenge is obligatory for immune responsiveness and immune memory, the IL-2-T cell system has opened the way to a molecular understanding of phenomena that are fundamental to biology, immunology, and medicine.
The effect of equisetin, an antibiotic produced by Fusarium equiseti, has been studied on mitochondrial functions (respiration, ATPase, ion transport). Equisetin inhibits the DNP-stimulated ATPase activity of rat liver mitochondria and mitoplasts in a concentration-dependent manner; 50% inhibition is caused by about 8 nmol equisetin/mg protein. The antibiotic is without effect either on the ATPase activity of submitochondrial particles or on the purified F1-ATPase. It inhibits both the ADP- or DNP-activated oxygen uptake by mitochondria in the presence of glutamate+malate or succinate as substrates, but only the ADP-stimulated respiration is inhibited if the electron donors are TMPD+ascorbate. It does not affect the NADH or succinate oxidation of submitochondrial particles. Equisetin inhibits in a concentration-dependent manner the active Ca(2+)-uptake of mitochondria energized both by ATP or succinate without affecting the Ca(2+)-uniporter itself. The antibiotic inhibits the ATP-uptake by mitochondria (50% inhibition at about 8 nmol equisetin/mg protein) and the Pi and dicarboxylate carrier. It does not lower the membrane potential at least up to 200 nmol/mg protein concentration. The data presented in this paper indicate that equisetin specifically inhibits the substrate anion carriers of the mitochondrial inner membrane.
Two factors that contribute to the progression of Parkinson disease are a brain defect in mitochondrial respiration and the generation of hydrogen peroxide (H2O2) by monoamine oxidase (MAO). Here we show that the two are linked. Metabolism of the neurotransmitter dopamine, or other monoamines (benzylamine, tyramine), by intact rat brain mitochondria suppresses pyruvate- and succinate-dependent electron transport. MAO inhibitors prevent this action. Mitochondrial damage is also reversed during electron flow. A probable explanation is that MAO-generated H2O2 oxidizes glutathione to glutathione disulfide (GSSG), which undergoes thiol-disulfide interchange to form protein mixed disulfides, thereby interfering reversibly with thiol-dependent enzymatic function. In agreement with this premise, direct addition of GSSG to mitochondria resulted in similar reversible inhibition of electron transport. In addition, the monoamines induced an elevation in protein mixed disulfides within mitochondria. These observations imply that (i) heightened activity and metabolism of neurotransmitter by monoamine neurons may affect neuronal function, and (ii) apparent defects in mitochondrial respiration associated with Parkinson disease may reflect, in part, an established increase in dopamine turnover. The experimental results also target mitochondrial repair mechanisms for further investigation and may, in time, lead to newer forms of therapy.
Cordyceps sinensis is a herb medicine with antitumor activity capable of suppressing the growth of mouse Sarcoma 180 in vivo. In the present study, we have isolated polysaccharide fraction of Cordyceps sinensis (PSCS) and investigated its effect on the proliferation and differentiation of human leukemic U937 cells using an in vitro culture system. Our results showed that the conditioned medium from PSCS (10 microg/ml)-stimulated blood mononuclear cells (PSCS-MNC-CM) had an activity that could significantly inhibit the proliferation of U937 cells resulting in a growth inhibition rate of 78-83%. Furthermore, PSCS-MNC-CM treatment induced about 50% of the cells differentiating into mature monocytes/macrophages expressing nonspecific esterase (NSE) activity and the surface antigens of CD11b, CD14, and CD 68. Yet, the differentiated U937 cells also had functions of phagocytosis and superoxide production. However, PSCS alone or normal MNC-CM had no such effects. The levels of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1 were very low in normal MNC-CM, and they were greatly increased in MNC-CM prepared with PSCS stimulation. Antibody neutralization studies further revealed that the tumoricidal and differentiating effects of PSCS-MNC-CM were mainly derived from the elevated cytokines, especially IFN-gamma and TNF-alpha. These two cytokines acted synergistically on inhibiting cell growth and inducing differentiation of the target U937 cells.
Cordyceps sinensis is one of the most valued herbs in traditional Chinese medicine. We investigated the antioxidant activities of the cultured fruiting bodies of Cordyceps sinesis. The water and ethanol extracts of Cordyceps sinensis were found to possess a potent antioxidant activity. The scavenging effects of the extracts on superoxide were very weak, but the extracts moderately inhibited malondialdehyde formation via hydroxyl radical induced by SIN-1, a peroxynitrite generator. Of the extracts examined, the hot water extract (70 degrees C for 5 min) showed the greatest oxygen free radical scavenging activity. Also, when low-density lipoprotein (LDL) was incubated with macrophages in the presence of CuCl2 (1 microM), the hot water extract showed a strong inhibitory effect against lipid peroxidation in the medium and consequent accumulation of cholesteryl ester in macrophages. Their activities were comparable to that of authentic Cu/Zn SOD. These results suggest that the extracts of cultured Cordyceps sinensis possess potent antioxidant and anti-lipid peroxidation activities and inhibit accumulation of cholesteryl ester in macrophages via suppression of LDL oxidation.
Cordyceps sinensis is a well-known traditional Chinese medicine, and some of the active components are nucleosides. The analysis of nucleosides in Cordyceps material has been performed by reversed-phase high-performance liquid chromatography (HPLC) with gradient elution or by spectrometry. Here, we have explored the possibility of using capillary electrophoresis to determine the content of three major nucleosides (adenosine, guanosine and uridine) in Cordyceps. Capillary electrophoresis needs no gradients, and it provides a better separation due to its higher efficiency. In order to optimize the resolution, the separation of adenosine, guanosine and uridine was determined in Cordyceps with respect to the variation of buffer concentration, pH, temperature, and voltage. By using the calibrated electrophoresis system, the separation was achieved for the three nucleosides in less than 10 min with a background electrolyte consisting of 0.2 M boric acid-sodium hydroxide buffer, pH 8.5. The nucleoside contents of various types of natural Cordyceps and cultured Cordyceps mycelia were determined and compared. There was a great variation of nucleoside content in different sources of Cordyceps; the cultured Cordyceps mycelia, however, contains a much higher concentration than the natural Cordyceps.
Cordyceps, one of the well-known traditional Chinese medicines, consists of the dried fungus Cordyceps sinensis growing on the larva of the caterpillar. It is commonly used for the replenishment of body health. One of the known pharmacological effects is its anti-oxidation activity. However, there is a great variation of the quality in different sources of Cordyceps. Here, the water extracts of various sources of natural C. sinensis and cultured Cordyceps mycelia were analyzed for their anti-oxidation activity by using three different assay methods such as the xanthine oxidase assay, the induction of hemolysis assay and the lipid peroxidation assay. The results showed that Cordyceps, in general, possesses a strong anti-oxidation activity in all assays tested. However, both natural and cultured Cordyceps showed the lowest inhibition in the lipid peroxidation when compared with the other two assay methods. The cultured Cordyceps mycelia had equally strong anti-oxidation activity as compared to the natural Cordyceps. Besides, the anti-oxidation activities were increased to 10-30 folds in the partially purified polysaccharide fractions from the cultured Cordyceps mycelia, which suggested that the activity could be derived partly from Cordyceps polysaccharides.
The effects of an orally administered hot-water extract (HW) from cultured mycelia of Cordyceps sinensis on the activation of macrophages and the intestinal immune system were studied in mice. The general composition of HW was 83.9% carbohydrate, 11.8% protein, 1.9% lipid and 2.4% ash, and the carbohydrates were mainly composed of glucose, mannose, galactose and arabinose (molar ratio of 1.0:0.8:0.5:0.1). HW stimulated the activation (1.7-fold of the saline control) of macrophages and IL-6 production (1.5-fold) at 2.0 g/kg/day. Analyzing the culture supernatant of Peyer's patch cells from C3H/HeJ mice that had been fed with HW at 1.0 g/kg/day for 7 days indicated that the bone marrow cells had significantly proliferated (1.9-fold). In addition, the amounts of GM-CSF and IL-6 in the culture supernatant of Peyer's patch cells at the same dose were significantly increased (1.8-fold and 2.2-fold, respectively). These results indicate that an oral administration of HW may modulate IL-6 production by the activation of macrophages, and also enhance the secretion of hematopoietic growth factors such as GM-CSF and IL-6 from Peyer's patch cells. Since such cytokines as GM-CSF and IL-6 from Peyer's patch cells act on the systemic immune system, it can be assumed that orally administered HW modulated not only the local but also systemic immune system.
Cordyceps pruinosa has been used in traditional folk medicine to treat numerous diseases. The molecular mechanism of C. pruinosa pharmacological and biochemical actions of macrophages in inflammation has not been clearly elucidated. We examined how the methanol extract of C. pruinosa regulates production of IL-1beta, TNF-alpha, nitric oxide (NO), and prostaglandin E(2) (PGE(2)) in vitro and in vivo. The extract inhibits these inflammatory mediators in LPS-stimulated murine macrophage cell line RAW264.7 and primary macrophages, by suppressing gene expression of IL-1beta, TNF-alpha, inducible nitric oxide synthase, and cyclooxygenase-2. Moreover, the extract suppresses the nuclear transcription factor NF-kappaB activation in LPS-stimulated RAW264.7 cells. Administration of the extract significantly decreases the plasma levels of these inflammatory mediators in LPS-injected mice. These results suggest that the C. pruinosa methanol extract suppresses inflammation through suppression of NF-kappaB-dependent inflammatory gene expression, suggesting that the C. pruinosa extract may be beneficial for treatment of endotoxin shock or sepsis.
The anti-tumor and immuno-stimulating activities of the fruiting bodies of Paecilomyces japonica (PJ), grown on silk-worm larvae and of Cordyceps sinensis (CS), a wild form of Cordyceps Fungi, were investigated. Ethanol extracts of both fungi, when administered for 9 consecutive days, at 50 and 100 mg/kg i.p., caused a significant increase in life span and a significant decrease in tumor weights and volumes, in mice inoculated with Sarcoma-180 tumor cells. Both fungal extracts were demonstrated to exhibit phagocytosis enhancing activity as measured by carbon clearance in mice. PJ extracts, when administered i.p. at 50 mg/kg/day for 3 consecutive days, exhibited a significant enhancement of phagocytosis, its potency as expressed by the regression coefficient ratio, RCtr/RCc, being 1.64 (the phagocytosis index = 2). This was approximately the same for that of zymosan (RCtr/RCc = 1.55, PI = 2), a typical phagocytosis enhancer, whereas CS extracts exhibited a moderate phagocytosis enhancing activity at the same dose level (RCtr/RCc = 1.30, PI = 1). Both fungal extracts caused a significant increase in an acid phosphatase activity, representing lysosomal enzymes, in macrophages at 20 and 100 micro g/ml in vitro, in compliance with in vivo results. These results suggest that the anti-tumor activity of both fungi might be related to an immuno-stimulating function.
Cordyceps sinensis, a well-known traditional Chinese medicine, possesses activities in anti-tumour, anti-oxidation and stimulating the immune system; however, the identity of active component(s) is not determined. By using anti-oxidation activity-guided fractionation, a polysaccharide of molecular weight approximately 210 kDa was isolated from cultured Cordyceps mycelia by ion-exchange and sizing chromatography. The isolated polysaccharide, having strong anti-oxidation activity, contains glucose, mannose and galactose in a ratio of 1 : 0.6 : 0.75. The pre-treatment of isolated polysaccharide on the cultured rat pheochromocytoma PC12 cells shows strong protective effect against hydrogen peroxide (H(2)O(2))-induced insult. Treatment of the cells with the isolated polysaccharide at 100 microg/ml prior to H(2)O(2) exposure significantly elevated the survival of PC12 cells in culture by over 60%. In parallel, the H(2)O(2)-induced production of malondialdehyde in cultured cells was markedly reduced by the polysaccharide treatment. Moreover, the pre-treatment of the isolated polysaccharide significantly attenuated the changes of glutathione peroxidase and superoxide dismutase activities in H(2)O(2)-treated cells in a dose-dependent manner. This is the first report in identifying a polysaccharide from Cordyceps, which protects against the free radical-induced neuronal cell toxicity.
The 'Yin-Yang' theory is an ancient Chinese philosophy that underlies the practice of traditional Chinese medicine. Although Yang-tonic herbs tend to boost body function possibly through enhancing the mitochondrial oxidative processes, the Yin property (i.e. antioxidant potential) of these herbs can also play a role in safeguarding mitochondrial ATP generation. The pharmacological basis of 'Yang-invigoration' by Chinese tonic herbs might be due primarily to the enhancement of mitochondrial ATP generation.
Practical Traditional Chinese Medicine and Pharmacology Basic Theories and Principles
- J Geng
- Z Su
Geng, J., Su, Z., 1991. Practical Traditional Chinese Medicine and Pharmacology, Volume 1: Basic Theories and Principles. New World Press, Beijing, China, pp. 208 – 234.
Interleukin-2: inception, impact, and implications
- Smith
Antioxidant activity of the extracts from fruiting bodies of cultured Cordyceps sinensis
- Yamaguchi