NSK Co., Ltd.
Pioneer of mycelium culture medium extracts

MAK Research

Suppresses colorectal tumors

Inhibitory effect of MAK on colon tumors induced by Azoxymethane (AOM) in rats

 

Hiroshima University

Rats were given AOM (15 mg/kg) subcutaneously once a week for a total of three times a week and fed a mixed diet of 1.25% MAK from 1 week before to 25 weeks after the start of treatment.
The results showed that MAK significantly reduced the incidence of colorectal tumors and the number of tumors per animal compared to the control group. These results suggest that MAK has an inhibitory effect on colorectal tumors.

 

Preventing Lung Cancer

Preventive effect of hot water extract of Ganoderma lucidum mycelium culture medium (MAK) on N-nitrosobis(2-hydroxypropyl)amine (BHP)-induced lung cancer modelGanoderma lucidum mycelium culture medium hot water extract (MAK)

 

Hiroshima University

The preventive effect of MAK on the carcinogenic process of lung cancer induced by BHP was investigated.
Rats were administered 0.2% BHP in drinking water for 10 weeks and then fed a mixed diet of 1.25% to 5% MAK for 12 weeks. They were then slaughtered and the number and size of nodules on the surface of the lung were measured. Tumor pathology (H, E) and immunohistology (PCNA, β-catenin) were also performed. The results showed that MAK dose-dependently reduced the number and size of tumors, but did not affect the incidence of tumors. In the PCNA index, MAK dose-dependently increased the number of negative tumors and decreased the number of moderately and strongly positive tumors. These results suggest that MAK has a preventive effect on lung cancer.

 


Anti-fatigue effect

Anti-fatigue effect of Ganoderma lucidum mycelium culture medium extract (MAK)

 

Josai University

In this study, we investigated the anti-fatigue effect of Ganoderma lucidum mycelium culture medium extract (MAK), which has antioxidant and anti-inflammatory properties. 1 g/kg/day of MAK was orally administered to SD rats for 1 week using a gastric tube. Citalopram was orally administered to the positive control group, and haloperidol was orally administered to the negative control group 60 min prior to fatigue loading.
Results showed that administration of MAK tended to prolong the swimming time in the forced swimming test and to increase the amount of spontaneous behavior after fatigue compared with the Control group. In addition, antidepressants (citalopram group) significantly prolonged the swimming time compared to the Control group.
In addition, the MAK group significantly suppressed the increase in blood lactate and oxidative stress levels and the decrease in liver and muscle glycogen levels after fatigue loading compared to the Control group, suggesting that MAK may have an anti-fatigue effect.

 


Suppression of blood glucose elevation

Suppressing the effect of MAK on elevated blood sugar

 

Josai University

The effect of MAK on the increase in blood glucose level was investigated. After oral administration of MAK to mice, we observed changes in blood glucose levels after glucose loading. The inhibitory activity of MAK on glycolytic enzymes was also investigated in vitro. In addition, we investigated the effect of MAK in combination with postprandial hyperglycemic agents (alpha-glucosidase inhibitors, voglibose).
In vitro, MAK inhibited maltase, α-amylase, and sucrase activities in a concentration-dependent manner. These results suggest that MAK inhibits carbohydrate degrading enzyme activity in the small intestine and decreases absorption of monosaccharides from the intestinal tract. In addition, in a glucose tolerance test using mice, no enhancement of the effect of the combination of the effective dose of voglibose (0.1 mg/kg) and MAK (1 g/kg) was observed, confirming the safety of simultaneous administration.

 

Investigation of the mechanism of inhibitory effect of [MAK] on elevated blood glucose level

 

Josai University

In order to elucidate the mechanism of the inhibitory effect of MAK, we investigated the effect of MAK on insulin secretion. After oral administration of MAK (2g/kg) to mice, glucose loading was performed, and blood insulin levels were measured. As a result, it was confirmed that maltose loading significantly increased blood insulin levels compared to the control group. These results suggest that the inhibitory effect of MAK on blood glucose elevation may be due to its inhibitory effect on sugar hydrolysis enzymes in the gastrointestinal tract of mice, as well as its stimulatory effect on insulin secretion.

Suppression of blood pressure elevation

Suppression of blood pressure elevation by extract of Ganoderma lucidum mycelium culture medium (MAK) in spontaneously hypertensive rats

 

Josai University

We investigated the inhibitory effect of MAK on blood pressure elevation in spontaneously hypertensive rats (SHR).
The control group was fed a normal diet and the MAK group was fed a mixed diet of 0.5% MAK for 10 weeks, and systolic blood pressure was measured. Real-time RT-PCR was then performed using total RNA extracted from the renal cortex, renal medulla, left ventricle, and abdominal aorta to measure PDGFa, TGFβ, and fibronectin mRNA levels.
The results showed that there was no difference in food intake and body weight in the MAK group compared to the control group, but there was a sustained and significant suppression of blood pressure elevation (approximately -20 mmHg) from the second week of food intake. In addition, the incidence of fibronection was reduced by about 50% in the left ventricle of the MAK group. These results suggest that MAK is expected to have an inhibitory effect on blood pressure elevation, and that this effect may contribute to reducing secondary cardiac risk.

 


brain damage

Protective effect of Ganoderma lucidum mycelium culture medium extract (MAK) on brain damage caused by transient cerebral ischemia in diabetic rats
 

Josai University

The protective effects of MAK against oxidative stress level and brain damage induced by transient ischemic treatment in streptozotocin (STZ) diabetic rats were compared with vitamin C (VC).
STZ diabetic rats were orally administered MAK (1 g/kg/day) or VC (100 mg/kg/day) for 2 weeks, and serum and brain tissue components were analyzed. Neurological scores and infarct volume (by TTC staining) were also measured after MCAO/RE (middle cerebral artery occlusion/reperfusion procedure) in rats. The results showed that the increase in oxidative stress level due to diabetes was suppressed in diabetic rats treated with MAK, and this effect was comparable to that of VC. In addition, the worsening of neurological symptoms and a marked increase in infarct volume after MCAO/RE were observed in diabetic rats compared to the normal group, but the exacerbation of these brain disorders was almost completely suppressed in diabetic rats orally treated with MAK or VC.
These results indicate that MAK reduces oxidative stress in diabetic conditions and has a strong cerebroprotective effect against brain damage caused by transient cerebral ischemia.

 

 

Analysis of the mechanism of cerebroprotective action of extracts from the culture medium of Ganoderma lucidum mycelium against ischemic brain damage in diabetic rats
 

Josai University

We investigated the brain protective mechanism of streptozotocin (STZ) in exacerbation of middle cerebral artery occlusion/reperfusion (MCAO/Re)-induced brain damage in diabetic rats. 50 mg/kg of STZ was intraperitoneally administered to SD rats (5W ♂) to produce diabetic (DM) rats, and citrate buffer solution was intraperitoneally administered to normoglycemic (non-DM) rats as the control group. The normoglycemic (non-DM) rats intraperitoneally treated with citrate buffer were used as the control group. After oral administration of MAK (1g/kg) or distilled water once a day for 2 weeks, antioxidant enzyme activity, lipid peroxide content, and neurological symptom scores at 3 and 24 hours after MCAO/Re treatment, as well as the volume of infarct foci by TTC staining, were measured in brain tissue.
The results showed that the MAK-treated group significantly reduced oxidative stress, improved lipid peroxide content and antioxidant enzyme activity in brain tissue to normal levels, and had an ameliorating effect on neurological symptoms and brain damage.

Inflammatory response during transient cerebral ischemia in rats using HMGB1 as an indicator and
Cerebroprotective effect of Reishi mycelium culture medium extract (MAK)
 

Josai University

The relationship between the protective effect of MAK on neurons and the behavior of HMGB1 (nucleoprotein) was investigated using in vitro cell culture experiments and a rat model of middle cerebral artery occlusion/reperfusion (MCAO/Re).
The results showed that the production of ROS was significantly decreased in hydrogen peroxide-treated PC12 cells pretreated with MAK, and the transfer of HMGB1 to the cytoplasm was also inhibited from low concentrations. These results indicate that MAK is protective against extracellular oxidative stress, inhibits intracellular ROS production, and suppresses HMGB1 release from low concentrations.
 Oral administration of MAK significantly suppressed the expression of pro-inflammatory cytokines such as IL-1β and TNF-α, and inhibited the migration/release of HMGB1 and activation of NF-κB by ischemic brain injury. B activation by ischemic brain injury.
 These results suggest that MAK acts as a scapenger against the overproduction of ROS and suppresses the expression of inflammation-related factors and the migration/release of HMGB1, thereby reducing the inflammatory response and exerting a brain protective effect.


dysphagia

Ameliorative Effect of Reishi Mushroom Mycelium Culture Medium Extract (MAK) on Dysphagia in Rats Treated with Chronic Cerebral Hypoperfusion
Ameliorative effect of Ganoderma lucidum mycelium culture medium extract (MAK) on dysphagia in rats treated with chronic cerebral hypovolemia

Josai University

We investigated the effect of MAK on improving swallowing. We prepared rats in which the common carotid artery was surgically ligated to reduce swallowing ability, and rats in which the carotid artery was only surgically ligated but not ligated (sham surgery group). The rats were administered MAK orally (1g/kg/day) for 2 weeks after surgery, and controls were given distilled water. Distilled water, citric acid, and capsaicin were used to induce swallowing.
The results showed that the swallowing ability of the MAK-treated group was restored to the same level as that of the sham-operated group receiving distilled water, indicating that MAK improves dysphagia. This effect was thought to be due in part to the fact that the decrease in the expression of tyrosine hydroxylase approached normal after administration of MAK, which was thought to play a role in the improvement of dysphagia.


depression

Evaluation of antidepressant effect of extracts from the culture medium of Ganoderma lucidum mycelium (MAK) by forced swimming test
 

Josai University

The antidepressant effect of MAK was investigated.
Results showed that MAK decreased immobility time in the forced swimming test, but had no effect on the amount of behavior in the open field test. These results suggest that the reduction in immobility time by MAK was not due to an increase in behavioral volume, but was due to its antidepressant effect.
In addition, the MAK-treated group showed an anxiolytic effect in the fear conditioning test and showed no significant change in the number of head twitches with 5-HT2 administration. On the other hand, MAK significantly reduced the number of head twitches induced by DOI, a 5-HT2 receptor agonist. These results suggest that MAK does not inhibit 5-HT reuptake and has a 5-HT2A receptor antagonist effect.
MAK has antidepressant effects, suggesting that its mechanism of action is partly related to its antagonism of 5-HT2A receptors.