KR102188202B1 - Composition for Preventing, Improving or Treating Cachexia and Muscle Loss - Google Patents

Abstract

The present invention relates to a composition comprising a rhubarb extract as an active ingredient, and the composition is useful for preventing, improving or treating cachexia and muscle loss because it reduces appetite, improves weight loss, muscle loss and fatigue, and suppresses hematopoietic toxicity. Can be used.

Description

Composition for preventing, improving or treating cachexia and muscle loss {Composition for Preventing, Improving or Treating Cachexia and Muscle Loss}

The present invention relates to a composition for preventing, improving, or treating cachexia and muscle loss, comprising a rhubarb extract as an active ingredient.

Cachexia is a syndrome that is common in chronic diseases such as cancer, tuberculosis, AIDS, and chronic obstructive pulmonary disease.It shows persistent loss of appetite and weight, resulting in malnutrition, metabolic imbalance, and muscle or fat loss. It refers to the catabolic state of metabolism in the body, and unlike other chronic diseases in the case of cancer patients, it is characterized by not only cachexia but also side effects of various chemotherapy methods used to treat cancer (Fearon K. et al., Lancet. Oncol 2011;12(5):489-495).

Cachexia occurs in 50-80% of gastrointestinal and lung cancer patients, and the mortality rate due to cachexia reaches 20-30%. Cancerous cachexia is characterized by weight loss by causing muscle loss due to an increase in catabolism caused by various cytokines and metabolic changes. These changes lower the response rate to chemotherapy or radiation therapy, make it difficult to proceed with effective chemotherapy, and lower the quality of life of the patient.

The mechanism of cachexia is a change in the activity of the neuroendocrine system, secretion of various inflammatory cytokines (IL-1beta, IL-6, TNF-α) and cancer-specific cachexia, and a decrease in food intake and metabolic changes. Known as. Among them, inflammatory cytokines are proteins that are secreted directly from tumors or produced by immune cells of the human body in response to tumors, and play an important role in immune control and play the most important role in the development of cachexia by causing loss of appetite and weight (Argiles JM, etc., Curr. Opin. Clin. Nutr. Metab. Care 1998; 1:245-251). Inflammatory cytokines are known to reduce appetite by causing changes in taste or gastrointestinal function (Durham WJ et al., Curr Opin Clin Nutr Metab Care. 2009; 12:72-77).

Muscle loss is one of the biggest features of cachexia, and is known to be due to the increase in protein catabolism and decrease in protein production due to overactivation of various cytokines. Cachexia is a symptom that includes muscle loss (myopenia) and has many overlapping parts. Most of the patients with cachexia have muscle loss (myopenia), but not all patients with muscle loss show cachexia symptoms. In clinical terms, muscle loss (myopenia) can be said to be a precursor symptom of cachexia. Inflammatory cytokines acting on cachexia affect insulin and testosterone, which regulate muscle metabolism, causing abnormal muscle protein synthesis (Seungwan Ryu, J. Clin. Nutr. 2017;9:2-6).

Currently, progesterone drugs (megesterol acetate; megace) and steroids (dexamethasone, prednisone) are used to treat cachexia, but steroids do not have a lasting therapeutic effect and have side effects such as water retention, insulin resistance, and adrenal function decline when used for a long time. Only short-term prescription is possible. Progesterone formulation (megace) was approved for use in AIDS patients showing anorexia or weight loss by the US FDA, and was currently approved for the treatment of cancerous cachexia in Korea, so it was used as a comparative drug of the present invention. However, it increases adipose tissue rather than muscle and has side effects such as erectile dysfunction, uterine bleeding, thromboembolism, edema, hyperglycemia, and adrenal function decline.

Patients with cachexia show a low response to chemotherapy and experience serious side effects. Chemotherapy methods for cancer patients include surgery, chemotherapy, and radiotherapy. Surgical surgery is a treatment method that removes lesions (ie, cancer). In the case of early cancer, it is possible to cure it only by surgical operation, but in the case of cancer after the middle stage, it is impossible to treat it with only surgery. Chemotherapy, radiation therapy, or combination therapy thereof is commonly used to remove target cancer cells by generating free radicals, but since they have low specificity, they also damage normal cells having the characteristics of rapidly dividing and proliferating such as hematopoietic cells or immune cells. Therefore, vomiting, loss of appetite, stomatitis, diarrhea, constipation, fever, infection, leukopenia, thrombocytopenia, anemia, abdominal pain, kidney toxicity, liver toxicity, heart toxicity, peripheral nerve toxicity, central nerve toxicity, muscle pain, bone pain, It causes side effects such as bone marrow suppression. Cachexia and muscle loss that occur with high frequency in cancer patients lowers the response rate to chemotherapy, makes it difficult to proceed with effective chemotherapy, and lowers the quality of life of the patient.

Therefore, in order to treat cachexia and muscle loss occurring in cancer and other diseases, there is a need to develop natural materials that are superior to existing therapeutic agents and safe for the human body.

1. Korean Patent Registration No. 10-1133837

One object of the present invention is to provide a pharmaceutical composition for preventing or treating cachexia and muscle loss comprising an extract of Rehmanniae Radix as an active ingredient.

Another object of the present invention is to provide a food composition for preventing or improving cachexia and muscle loss, comprising a rhubarb extract as an active ingredient.

Another object of the present invention is to provide an anticancer adjuvant comprising a pharmaceutical composition for preventing or treating cachexia and muscle loss, comprising a rhubarb extract as an active ingredient.

In order to achieve the above object, one aspect of the present invention provides a pharmaceutical composition for preventing or treating cachexia and muscle loss, comprising a rhubarb extract as an active ingredient.

The term'cachexia' as used herein refers to a high degree of systemic weakness that can be seen at the end of cancer, tuberculosis, diabetes, and acquired immunodeficiency syndrome (AIDS), and gastric cancer, esophageal cancer, colon cancer, etc. It is often seen in cancer patients and lung cancer patients. It shows symptoms such as decreased appetite, weight and physical strength, anemia, lethargy, and indigestion. In particular, it is difficult to eat normal food due to decreased appetite, or it indicates a condition in which weight is decreased even if normal food is consumed. When cachexia occurs, the patient's quality of life decreases as it shows a low response to chemotherapy or radiation therapy, resulting in a shortening of life expectancy, and causes death due to weight loss in 10 to 20% of all cancer patients. do.

As used herein, the term'muscle loss' refers to a decrease in muscle in the body, for example, reduction of muscle tissue caused by not using muscle, and muscle tissue due to a disease of the muscle itself. It may be a decrease or a decrease in muscle tissue due to damage to the nerves that dominate the muscle, and such muscle loss may be caused by, for example, cachexia or muscle atrophy.

According to an embodiment of the present invention, the cachexia may be caused by cancer, and on the other hand, it may be caused by an anticancer agent used for cancer treatment. The anticancer agent is selected from the group consisting of doxorubicin, irinotecan, paclitaxel, daunorubicin, docetaxel, cisplatin, and 5-fluorouracil. Can be.

Rehmanniae Radix used as an active ingredient of this composition corresponds to the Korean Pharmacopoeia standard and is the root of Rehmannia glutinosa Liboschitz ex Steudel, a plant in the Scrophulariaceae family . In oriental medicine, the raw material of the root is called Saengjihwang, the dried one is called Geonjihwang, and the steamed and dried one is called Sukjihwang. Saengjihwang is used for constipation, Geonjihwang is used for thirst quenching, and Sukjihwang is known to be effective in dementia. However, little is known about the effects of improving cachexia, such as improving appetite reduction and suppressing muscle loss.

According to one embodiment of the present invention, the rhubarb extract may be prepared according to a conventional method known in the art. For example, after pulverizing the rhubarb, a solvent commonly used for extraction may be added, and extraction may be performed at an appropriate temperature and pressure to prepare an extract of rhubarb.

According to one embodiment of the present invention, the solvent may be selected from the group consisting of distilled water, C ₁ to C ₄ lower alcohol, hexane, ethyl acetate, chloroform, diethyl ether, dichloromethane, acetone, and mixtures thereof. .

On the other hand, the Rehmannia extract includes not only the extract by the solvent extraction method described above, but also an extract that has undergone a conventional purification process. For example, through a variety of additional purification methods, such as separation using an ultrafiltration membrane having a certain molecular weight cut-off value, separation by various chromatography (made for separation according to size, charge, hydrophobicity, or affinity). The obtained fraction may also be included in the extract of the present invention. In addition, the extract may be prepared in a powder state by an additional process such as distillation under reduced pressure and freeze drying or spray drying.

According to one embodiment of the present invention, since the rhubarb extract can improve symptoms selected from the group consisting of decreased appetite, reduced weight, increased fatigue, increased inflammation, muscle loss and hematopoietic toxicity, improved cachexia and muscle loss, prevention Or it can be usefully used for therapeutic purposes.

For administration, the pharmaceutical composition may be preferably formulated as a pharmaceutical composition, including at least one pharmaceutically acceptable carrier in addition to the above-described extract of rhubarb.

The formulation form of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops, or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders are, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, lacquercanth or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.

As acceptable pharmaceutical carriers for compositions formulated as liquid solutions, sterilization and biocompatible, saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added as necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare injectable formulations such as aqueous solutions, suspensions, emulsions, and the like, pills, capsules, granules, or tablets.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, or the like.

A suitable dosage of the pharmaceutical composition of the present invention can be determined by factors such as formulation method, mode of administration, age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate and response sensitivity of the patient. . According to one embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.001 to 10 g/kg.

The pharmaceutical composition of the present invention is prepared in unit dosage form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily carried out by a person having ordinary knowledge in the technical field to which the present invention belongs. Or it can be made by incorporating it into a multi-dose container.

Another aspect of the present invention provides a food composition for preventing or improving cachexia and muscle loss comprising an extract of Rehmanniae Radix as an active ingredient.

The food composition according to the present invention may be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, confectionery, diet bars, dairy products, meat, chocolate, pizza, ramen, other noodles, gums, ice creams, vitamin complexes, health supplements, etc. .

The food composition of the present invention may include ingredients that are commonly added during food production in addition to containing a rhubarb extract as an active ingredient, and include, for example, proteins, carbohydrates, fats, nutrients, flavoring agents and flavoring agents. . Examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)] and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is made of drinks and beverages, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts, etc. may be additionally included in addition to the rhubarb extract of the present invention. have.

Another aspect of the present invention provides an anticancer adjuvant comprising a pharmaceutical composition for preventing or treating cachexia and muscle loss as an active ingredient.

As used herein, the term'anticancer adjuvant' refers to an adjuvant showing an effect of improving the side effects of an anticancer agent during anticancer treatment, and side effects of the anticancer agent include hematopoietic toxicity, decreased appetite, muscle loss, endurance reduction, weight loss, etc. Can be included.

The anticancer adjuvant may further include at least one active ingredient exhibiting the same or similar function in addition to including the extract of Reichstag as an active ingredient. The anticancer adjuvant can be administered orally or parenterally at the time of clinical administration, and when administered parenterally, intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine dural injection, cerebrovascular injection or chest It can be administered by intramuscular injection, and can be used in the form of a general pharmaceutical formulation.

The anticancer adjuvant may be used alone or in combination with surgery, radiation therapy, hormone therapy, chemotherapy, and methods using biological response modifiers. The daily dosage of the anticancer adjuvant is about 0.0001 to 1000 mg/kg, preferably 1 to 100 mg/kg, and it is preferable to administer once to several times a day, but the weight, age, sex, health status of the patient, The range varies according to diet, administration time, administration method, excretion rate, and severity of disease. The anticancer adjuvant of the present invention can be administered in various parenteral formulations at the time of actual clinical administration.When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants are used. It is prepared. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like may be used.

The composition comprising the extract of Rehmannia rhubarb as an active ingredient reduces appetite, reduces weight, improves muscle loss and fatigue, and suppresses hematopoietic toxicity, so it can be usefully used for preventing, improving, or treating cachexia and muscle loss.

1 is a result of measuring dietary amount, tumor weight, serum and intramuscular TNF-α concentration, and intramuscular IL-6 concentration after administering a rhubarb extract to a mouse induced tumor with MC38 colon cancer cells and a forced swimming test Shows the result of execution.
FIG. 2 shows the results of measuring dietary amount, tumor weight, and intramuscular IL-1β concentration after administration of a rhubarb extract to mice induced tumors with B16BL6 melanoma cells, as well as the results of a forced swimming test.
Figure 3 shows the results of measuring dietary amount, body weight, and glycogen content in muscles after administering a rhubarb extract to a mouse inducing anticancer side effects, and a result of performing a forced swimming test.
Figure 4 shows the results of blood analysis after administering a rhubarb extract to a mouse induced anticancer side effects.

Hereinafter, one or more specific examples will be described in more detail through examples. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.

Example 1. Preparation of Rehmannia Root Extract

250 g of Rehmanniae Radix and 2L of 30% ethanol were added to a 3L reactor, and extracted under reflux for 4 hours at 65°C using a reflux extractor. The primary extract was filtered, and 2L of 30% ethanol was added to the residue, followed by secondary extraction under the same conditions. Thereafter, the second extract was filtered, mixed with the first extract, and concentrated at 50° C. or lower to remove ethanol. The concentrated extract was lyophilized and then homogenized by grinding with a blender. As a result of preparation of the extract, a dry weight of 116 g (yield 46.40%) of a rhubarb extract was obtained.

Example 2. Confirmation of the effect of improving cachexia and muscle loss by tumor

2-1. Experimental animals and experimental methods

Experimental animals were 4-week-old male C57BL/6 mice (18 to 20 g), supplied from Central Experimental Animal Co., Ltd. and used for experiments after being acclimated for 1 week in an experimental animal breeding ground. During the experiment period, solid feed and water were freely ingested, and the temperature (22±2℃), relative humidity (60±5%) and brightness of the breeding room were maintained at a 12-hour cycle.

The mice were divided into 9 mice for each group into a normal group, a control group (control, tumor-inducing group), a conventional drug administration group, and a rhizome extract administration group. In the normal group, 100 µl of PBS was injected subcutaneously, and the tumor-causing group (control group), conventional MC38 (1×10 ⁶ cells/100 μl) colon cancer cells or B16BL6 (1×10 ⁶ cells/100 μl) melanoma cells were subcutaneously injected into the drug administration group and the Rehmannia extract administration group. After inducing the tumor for 2 weeks, when the tumor volume reached about 1000 3, Megace (Megestrol acetate) 125 mg/kg (=625 mg), the cancer cachexia treatment most commonly used in clinical practice, was used in the existing drug administration group. [Daily human dose] / 60kg [human average weight] x 12 [dose equivalent factor compared to human body surface area compared to human]) was orally administered for 14 days, and the Rehmannia extract prepared in Example 1 was administered in Megace dose It was orally administered for 14 days at a slightly smaller dose, 100 mg/kg. During the experiment, the dietary amount of the mice was recorded, and after the experiment was completed, the mice were sacrificed and blooded, the tumor size was checked, and serum and intramuscular TNF-α, IL-6 and IL-1β were determined by ELISA. Quantified.

2-2. Appetite Improvement Effect of Rehmannia Root Extract

After inducing the tumor, the dietary amount of the mice was recorded while oral administration of the Rehmannia extract for 14 days. As a result, as disclosed in Table 1 and FIGS. 1 and 2 below, it was confirmed that the amount of diet was increased in the group administered with rhizome extract compared to the tumor inducing group (control group). ^* P<0.05 in Table 1 below; ^** p<0.01; And ^*** p<0.001, and were used in the same meaning in the tables and drawings described below.

Dietary amount (g) Mean±standard deviation p-value: compared to control
unpaired t-test MC38 Normal 3.199±0.509 0.006 ^** Control group (tumor inducing group) 2.635±0.523 1.000 Conventional drug administration group 2.724±0.482 0.638 Rehmannia extract administration group 3.013±0.447 ^* 0.042 ^* B16BL6 Normal 3.680±0.555 0.001 ^** Control group (tumor inducing group) 2.594±0.409 1.000 Conventional drug administration group 3.005±0.436 0.069 Rehmannia extract administration group 3.138±0.573 ^* 0.048 ^*

2-3. Confirmation of changes in tumor size of Rehmannia extract

After inducing the tumor, a rhizome extract was orally administered for 14 days, and then the mouse was sacrificed to confirm the tumor size. As a result, as disclosed in Table 2 and FIGS. 1 and 2 below, it was confirmed that there was no significant change in tumor size in the group administered with the rhubarb extract compared to the tumor inducing group (control group).

That is, it was confirmed that the effect of improving cachexia and muscle loss of the extract of Rehmannia was not due to the anticancer effect.

Tumor weight (g) Mean±standard deviation p-value: compared to control
unpaired t-test MC38 Control group (tumor inducing group) 5.059±3.317 1.000 Conventional drug administration group 3.921±1.231 0.382 Rehmannia extract administration group 6.147±2.009 0.429 B16BL6 Control group (tumor inducing group) 8.777±3.132 1.000 Conventional drug administration group 8.728±2.284 0.972 Rehmannia extract administration group 7.668±2.490 0.477

2-4. Effect of Rehmannia Root Extract to Prevent Muscle Loss

After the tumor was induced, a rhubarb extract was administered orally for 14 days, and then the mice were sacrificed to check the concentration of serum and intramuscular inflammatory cytokines. As a result, as shown in Table 3 and FIGS. 1 and 2 below, inflammatory cytokines were increased by tumor in the control group (tumor-inducing group) compared to the normal group, and serum and serum and It was confirmed that intramuscular inflammatory cytokines were reduced, and the effect of improving inflammation and muscle loss of the extract of Rehmannia was confirmed.

Cytokine concentration (pg/ml) Mean±standard deviation p-value: compared to control
unpaired t-test MC38 serum
TNF-α
Normal 78.467±18.762 0.003 ^** Control group (tumor inducing group) 120.943±28.139 1.000 Conventional drug administration group 87.550±22.050 ^* 0.023 ^* Rehmannia extract administration group 67.356±33.568 ^** 0.004 ^** Intramuscular
TNF-α
Normal 30.318±1.874 0.083 Control group (tumor inducing group) 42.091±11.380 1.000 Conventional drug administration group 16.758±7.333 ^** 0.003 ^** Rehmannia extract administration group 20.870±10.358 ^* 0.013 ^* Intramuscular
IL-6
Normal 60.600±10.733 0.010 ^** Control group (tumor inducing group) 79.800±6.986 1.000 Conventional drug administration group 66.400±16.371 0.138 Rehmannia extract administration group 61.000±7.925 ^** 0.004 ^** B16BL6 Intramuscular
IL-1β
Normal 160.093±9.228 0.000 ^*** Control group (tumor inducing group) 317.060±35.208 - Conventional drug administration group 278.851±11.658 ^* 0.013 ^* Rehmannia extract administration group 282.292±17.271 ^* 0.031 ^*

2-5. Fatigue Improvement Effect of Rehmannia Root Extract

On the 12th day after oral administration of a conventional drug or a rhubarb extract to the tumor-inducing mouse, the mice's fatigue level was confirmed by a forced swimming test. The normal group was loaded with a weight corresponding to the average weight of the tumor, and the other group was not loaded with a separate weight because the tumor itself acts as a load. As a result of the measurement, as shown in Table 4 below and FIGS. 1 and 2, it was confirmed that the swimming time was significantly reduced in the control group compared to the normal group, and the fatigue was remarkable. On the other hand, compared to the control group, it was confirmed that the swimming time was significantly increased in the group administered with the extract of Rehmannia, and the fatigue of the tumor-induced mice was improved.

Swimming time (seconds) Mean±standard deviation p-value: compared to control
unpaired t-test MC38 Normal 420.0±89.5 0.002 ^** Control group (tumor inducing group) 137.4±80.9 1.000 Conventional drug administration group 249.3±149.5 0.151 Rehmannia extract administration group 312.3±134.3 0.028 ^* B16BL6 Normal 332.1±107.4 0.009 ^** Control group (tumor inducing group) 136.5±105.6 1.000 Conventional drug administration group 323.4±125.3 0.029 ^* Rehmannia extract administration group 303.3±35.0 0.024 ^*

Example 3. Checking the effect of improving cachexia and muscle loss by anticancer agents

3-1. Experimental animals

Experimental animals were 4-week-old male C57BL/6 mice (18 to 20 g), supplied from Central Experimental Animal Co., Ltd. and used for experiments after being acclimated for 1 week in an experimental animal breeding ground. During the experiment period, solid feed and water were freely ingested, and the temperature (22±2℃), relative humidity (60±5%) and brightness of the breeding room were maintained at a 12-hour cycle.

Mice were divided into 9 mice for each group into a normal group, a control group, and a group administered with rhizome extract. Except for the normal group, the remaining groups included 5-fluorouracil, an anticancer drug commonly used for cancer of the digestive system; Hereinafter, 5-FU) was administered once intraperitoneally at a concentration of 200 mg/kg to induce anticancer side effects. After 7 days of 5-FU administration, distilled water (control) or rhubarb extract (500 mg/kg) was orally administered to each group for 7 days, and the dietary amount of the mice was recorded during the experiment.

3-2. Effect of Rehmannia Root Extract on Weight and Appetite Improvement

For 7 days after 5-FU administration, the dietary amount of the mice was recorded while oral administration of the Rehmannia extract (500 mg/kg). As a result, as shown in Table 5 and FIG. 3 below, it was confirmed that body weight and dietary amount were significantly reduced in the control group compared to the normal group, but the body weight and dietary amount were recovered in the Rehmannia extract administration group.

Mean±standard deviation p-value: compared to control
unpaired t-test Normal Control Rehmannia extract
Administration group Normal Control Rehmannia extract
Administration group Weight (g) 20.545±
0.919 ^*** 18.243±
1.394 20.010±
1.706 ^* 0.0007 ^*** 1.000 0.03485 ^* Dietary amount (g) 2.798±
0.151 ^** 2.359±
0.042 2.648±
0.102 ^** 0.0049 ^** 1.000 0.00628 ^**

3-3. Effect of Rehmannia Root Extract to Prevent Muscle Loss

After the end of the experiment, the muscle was separated from the thigh of the mouse, and the glycogen component (muscleglycogen) present in the muscle was measured according to a method known in the art.

As a result of the measurement, as shown in Table 6 below, glycogen was significantly reduced in the control group compared to the normal group, but it was confirmed that the glycogen concentration was recovered by administration of the Rehmannia extract.

Mean±standard deviation p-value: compared to control
unpairedt-test Normal Control Rehmannia extract
Administration group Normal Control Rehmannia extract
Administration group Muscle Glycogen
(㎍/mg tissue) 95.194±
46.169 64.008±
2.993 94.077±
7.599 ^** 0.227 1.000 0.001 ^**

3-4. Fatigue Improvement Effect of Rehmannia Root Extract

On the 6th day after oral administration of rhubarb extract to the mice inducing anticancer side effects, the fatigue of the mice was confirmed by a forced swimming test, and the swimming time was measured after loading about 5% of the mouse weight.

As a result of the measurement, as shown in Table 7 and FIG. 3, it was confirmed that the swimming time was significantly reduced in the control group compared to the normal group, and the fatigue was remarkable. On the other hand, compared to the control group, it was confirmed that the swimming time was significantly increased in the group administered with the extract of Rembranaceus, indicating that the fatigue of the mice induced with anticancer side effects was improved.

Mean±standard deviation p-value: compared to control
unpaired t-test Normal Control Rehmannia extract
Administration group Normal Control Rehmannia extract
Administration group Swimming time (sec) 89.000±
73.980 ^** 19.100±
9.218 129.600±
154.209 ^* 0.0083 ^** 1.000 0.03631 ^*

3-5. Hematopoietic Function Improvement Effect of Rehmannia Root Extract

After oral administration of the Rehmannia rhizome extract for 7 days, blood was separated from the mice and analyzed with a hemocytometer. As a result of the analysis, it was confirmed that the number of white blood cells (WBCs) and lymphocytes (lymphocytes) was significantly increased in the group to which the rhubarb extract was administered as compared to the control group as shown in Table 8 and FIG. 4 below. In addition, it was found that the number of platelets and red blood cells, and hemoglobin levels were increased in the group administered with the extract of Rehmannia.

ingredient Normal Control Rehmannia extract
Administration group p-value: compared to control
unpaired t-test Normal Control Rehmannia extract
Administration group leukocyte
(x10 ³ cells/µl) 4.292±
0.761 ^*** 0.674±
0.267 2.114±
1.310 ^* 0.0000 ^*** 1.000 0.0427 ^* Lymphocyte (x10 ³ cells/µl) 3.284±
1.009 ^*** 0.476±
0.263 1.846±
1.139 ^* 0.0003 ^*** 1.000 0.0307 ^* Red blood cells (x10 ⁶ cells/µl) 9.166±
0.513 ^*** 6.238±
0.394 7.092±
1.239 0.0000 ^*** 1.000 0.1803 Hemoglobin (g/dL) 13.660±
1.071 ^*** 8.940±
0.684 10.340±
1.660 0.0000 ^*** 1.000 0.1195 Platelets (x10 ³ cells/µl) 1156.200±
168.637 ^*** 332.200±
136.867 720.400±
431.848 0.0000 ^*** 1.000 0.0917

So far, the present invention has been looked at around its preferred embodiments. Those of ordinary skill in the art to which the present invention pertains will be able to understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative point of view rather than a limiting point of view. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the scope equivalent thereto should be construed as being included in the present invention.

Claims (7)

In the pharmaceutical composition for preventing or treating cachexia or muscle loss comprising an ethanol extract of Rehmanniae Radix as an active ingredient,
The composition is a pharmaceutical composition for preventing or treating cachexia or muscle loss that decreases the level of TNF-α.
delete The pharmaceutical composition for preventing or treating cachexia or muscle loss according to claim 1, wherein the cachexia is caused by cancer.
The pharmaceutical composition for preventing or treating cachexia or muscle loss according to claim 1, wherein the cachexia is caused by an anticancer agent.
The pharmaceutical composition for preventing or treating cachexia or muscle loss according to claim 1, wherein the composition improves symptoms selected from the group consisting of decreased appetite, weight loss, increased fatigue, increased inflammation, muscle loss and hematopoietic toxicity.
In the food composition for preventing or improving cachexia or muscle loss containing ethanol extract of Rehmanniae Radix as an active ingredient,
The composition is a food composition for preventing or improving cachexia or muscle loss to reduce the level of TNF-α.
An anticancer adjuvant comprising the composition of claim 1 as an active ingredient.

Images