Differential Effects of Yin- and Yang-Chinese Tonifying Herbs on Innate and Adaptive Immunity

The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive immunity) and natural killer (NK) cell activity (innate immunity) in an ex vivo mouse model. The results indicated that while treatment with most Yin herbal extracts potentiated the Con A/LPS-stimulated splenocyte proliferation, only Yang (but not Yin) herbal extracts stimulated NK cell activity. The differential effects of Yin- and Yang-Chinese tonifying herbs on innate and adaptive immunity are consistent with the Chinese medicine theory which depicts the Yin and Yang functional components of Zheng Qi (vital energy), with the Yang component being responsible for the first line of defense against invading microorganisms (i.e., innate immunity) and the Yin oner serving as a follow-up defensive response (adaptive immunity).

Differential Effects of Ursolic Acid and Oleanolic Acid on Mitochondrial ATP Generation in H9c2 Cardiomyocytes and Lipopolysaccharide-Induced Cell Proliferation in Mouse Splenocytes: Yang versus Yin

In the present study, two cell-based systems for assessing Yang and Yin activities were for the first time used to investigate the effect of ursolic acid (UA) and oleanolic acid (OA). The results indicated that while UA was only active in the Yang assay, OA produced activity in the Yin assay. The Yang/Yin activity of UA/OA may be attributed to their distinct molecular structures, which confer their differential ability to interact with mitochondrial membrane or cellular membrane lipids, with resultant membrane fluidization and potentiation of biological responses.

‘Yang-Invigorating’ Chinese Tonic Herbs Enhance Mitochondrial ATP Generation in H9c2 Cardiomyocytes

‘Yang-invigorating’ Chinese tonic herbs have been shown to enhance the myocardial mitochondrial ATP generation capacity in mice ex vivo. In the present study, we examined the effect of treatment with the methanol extract of ‘Yang-invigorating’ herbs on mitochondrial ATP generation capacity in H9c2 cardio-myocytes. The effect of ‘Yin-nourishing’ herbs was also investigated for comparison. The results indicated that all ‘Yang-invigorating’ Chinese tonic herbs dose-dependently enhanced the mitochondrial ATP genera-tion capacity in H9c2 cardiomyocytes. Three out of nine ‘Yin-nourishing’ herbs produced a dose-dependent stimulatory effect on ATP generation, but to lesser extents than those of Yang herbs. Results obtained from activity-directed fractionation of the three most potent ‘Yang-invigorating’ herbs suggested that the ATP-stimulating ingredients were rather water insoluble and largely resided in the butanol fraction. In con-clusion, ‘Yang-invigorating’ herbs invariably stimulated mitochondrial ATP generation capacity in H9c2 cardiomyocytes. The cell-based assay of ATP generation capacity may be used as pharmacological test for ‘Yang-invigorating’ Chinese tonic herbs.

Pharmacological Investigation on the Qi-Invigorating Action of Schisandrin B: Effects on Mitochondrial ATP Generation in Multiple Tissues and Innate/Adaptive Immunity in Mice

Schisandrae Fructus, containing schisandrin B (Sch B) as its main active component, is recognized in traditional Chinese medicine (TCM) for its Qi-invigorating properties in the five visceral organs. Our laboratory has shown that the Qi-invigorating action of Chinese tonifying herbs is linked to increased mitochondrial ATP generation and an enhancement in mitochondrial glutathione redox status. To explore whether Sch B can exert Qi-invigorating actions across various tissues, we investigated the effects of Sch B treatment on mitochondrial ATP generation and glutathione redox status in multiple mouse tissues ex vivo. In line with TCM theory, which posits that Zheng Qi generation relies on the Qi function of the visceral organs, we also examined Sch B’s impact on natural killer cell activity and antigen-induced splenocyte proliferation, both serving as indirect measures of Zheng Qi. Our findings revealed that Sch B treatment consistently enhanced mitochondrial ATP generation and improved mitochondrial glutathione redox status in mouse tissues. This boost in mitochondrial function was associated with stimulated innate and adaptive immune responses, marked by increased natural killer cell activity and antigen-induced T/B cell proliferation, potentially through the increased generation of Zheng Qi.

Differences in the Mechanisms by Which Yang-Invigorating and Qi-Invigorating Chinese Tonifying Herbs Stimulate Mitochondrial ATP Generation Capacity

According to Chinese medicine theory, Yang/Qi plays a pivotal role in driving physiological functions in the body, these being highly dependent on mitochondrial ATP production. Consistent with this, Yang/Qi-invigorating Chinese tonifying herbs have been found to stimulate mitochondrial ATP generation capacity (ATP-GC) in H9c2 cardiomyocytes. In the present study, we have demonstrated that Yang-invigorating Chinese tonifying herbs (namely, Eucommiae Cortex, Cibotii Rhizoma, Dipsaci Radix, Cynomorii Herba, Cistanches Herba, Cuscutae Semen, EpimediiHerba and Morindae Radix) and Qi-invigorating Chinese tonifying herbs (namely, Ginseng Radix, Pseudostellariae Radix, Quinquefolii Radix, Codonopsis Radix, Astragali Radix, Atractylodis Rhizoma, Juiubae Fructus, Fici Simplicissimae Radix and Dioscoreae Oppositae Radix) act by different mechanisms to stimulate mitochondrial ATP-GC. While Yang-invigorating herbs fluidize mitochondrial membranes and thus stimulate ATP-GC, Qi-invigorating herbs can enhance cellular glutathione status and increase ATP-GC. The different mechanisms by which Yang-invigorating herbs and Qi-invigorating herbs stimulate mitochondrial ATP-GC may serve as the basis for establishing biomarkers for Yang/Qi-invigorating herbs and herbal health products in general.

An Ultimate Approach to Retarding the Aging Process by Integrating Traditional Chinese Medicine and Western Medicine

Aging and death are unavoidable in life. While immortality may be impossible, many people dream of living a long and healthy life. Throughout history, humans have searched for ways to stay young, but have not found an effective way. This may be because the methods used do not target the causes of aging directly. To address this, we investigated how to delay aging using traditional Chinese medicine (TCM) and Western medicine approaches. In this article, we will explain the causes of aging in the context of TCM and Western medicine and suggest methods to delay it. By integrating TCM and Western medicine, I hope to help everyone age healthily and enjoy a long life.

The Essential Role of Zheng Qi in Promoting Health: From the Perspective of Chinese Medicine and Modern Medicine

The concept of Zheng Qi in traditional Chinese medicine (TCM) refers to the vital energy produced by the interaction of Yin and Yang forces in the body. Zheng Qi performs two main functions: Wei Qi (defensive Qi), which shields the body from external pathogens, and Ying Qi (nutritive Qi), which sustains the internal organs and enhances their functionality. In TCM, Chinese tonifying herbs can help restore the balance of Yin/Yang and Qi/Blood function in visceral organs (i.e., optimal physiological functions), thereby fostering the efficient production of Zheng Qi and enhancing health. To ensure the quality of Chinese herbal products, functional assays to measure Yin/Yang, Qi/Blood functions, and Zheng Qi production should be implemented. The efficacy of Yang and Qi herbs can be evaluated by their ability to increase mitochondrial ATP in cultured mouse cardiomyocytes, while Yin and Blood herbs are tested through their immunostimulatory effects on antigen-induced T/B cell proliferation in mouse splenocytes and the production of erythropoietin/nitric oxide in hepatocytes/vascular endothelial cells, respectively. Additionally, Zheng Qi’s effect can be gauged by examining natural killer cell activity and antigen-induced T/B cell proliferation in mice ex vivo. These assays act as biomarkers for assessing the quality and effectiveness of herbal health products within TCM theory.

How Schisandrae Fructus Benefits the Body: Mechanisms in Traditional Chinese Medicine and Modern Medicine

Schisandrae chinensis Fructus (SF) is a commonly used herb in Traditional Chinese Medicine (TCM). According to TCM theory, SF can invigorate Qi in the liver and other visceral organs through the meridian system. Furthermore, the liver’s pivotal role in regulating the functions of various visceral organs helps explain how SF can promote holistic health benefits. The main active ingredient of SF, schisandrin B (Sch B), has been found to improve mitochondrial ATP production and enhance glutathione redox status in multiple organs. This could account for the overall protective effects of Sch B on organs. Due to its stronger impact on liver function, the positive influence of Sch B on different organs may be facilitated by signal molecules originating from the liver.

An Herbal Formula (GPC) Suppresses the Releases of Pro-Inflammatory Effectors in Lipopolysaccharide/Peptidoglycan-Activated RAW264.7 Macrophages and Reduces the Extent of Chemical-Induced Acute/Chronic Inflammation in Rodents

Pharyngitis (an inflammation in the pharynx) is a commonly occurring symptom of upper respiratory tract infection in patients suffering from common cold. The high prevalence of upper respiratory tract infection necessitates a safe and effective antiinflammatory agent for pharyngitis. Chinese herbal medicine, which has been clinically prescribed for thousands of years, may offer a basis for the treatment of common cold as well as the amelioration of pharyngitis. In the present study, we investigated the in vitro and in vivo anti-inflammatory activities of a Chinese herbal formula, namely GPC, which is comprised of Glycyrrhiza Radix, Platycodonis Radix, Citri Reticulatae Pericarpium, Phyllanthi Fructus and Taraxaci Herba. Incubation with GPC (30, 100 and 300 μg/mL) suppressed the releases of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and nitric oxide in lipopolysaccharide/peptidoglycanactivated RAW264.7 macrophages. In addition to the cell-based study, long-term treatment with GPC (0.35, 1.05 and 2.10 mL/kg/day × 30 doses) was found to reduce the extent of inflammation in animal models of carrageenan-induced paw edema (acute inflammation) as well as cotton pellet-induced granuloma formation (chronic inflammation) in mice. The ability of GPC to enhance the tracheobronchial expectorant action suggested its immunomodulatory activity in the respiratory tract. This postulation was supported by the observation that GPC reduced the degree of pharyngitis and reversed the changes in plasma TNF-α and IL-6 levels in capsaicininduced pharyngitis in rats. The ensemble of results suggests that GPC may offer a promising prospect for alleviating the extent of pharyngitis by virtue of antiinflammatory activities.

Cell-Based Biological Markers for Blood-Enriching Chinese Herbs: Erythropoietin Production in HepG2 Cells and Nitric Oxide Release in Human Umbilical Vein Endothelial Cells (HUVECs)

Chinese tonifying herbs, which are classified into four functional categories (namely, Yang, Qi, Yin, Blood) are commonly used for restoring normal body function and the prevention of diseases. To explore cell-based biological markers for Blood-enriching Chinese herbs, we investigate the effect of 11 commonly used Blood-enriching herbs on erythropoietin (EPO) production in HepG2 cells. Herbs for nourishing Yin were tested for determining the specificity of Blood-enriching herbs in inducing EPO production. In addition, the effects of Blood-enriching herbs on nitric oxide (NO) production in both HepG2 cells and human umbilical vein endothelial cells (HUVECs) were also investigated. The results indicated that methanolic extracts of Blood-enriching herbs (but not Yin-nourishing herbs) showed characteristic pharmacological activity in inducing EPO production in HepG2 cells and NO release in HUVECs. The experimental findings, therefore, support the use of cell-based EPO production and NO release as biological markers for Blood-enriching Chinese tonifying herbs.

A Cardiomyopeptin Preparation Protects against Isoproterenol-Induced Chronic Heart Failure in Rats

The present study investigated the effect of an herbal extract-supplemented cardiomyopeptin preparation (HECP), in the rat model of chronic heart failure. HECP pre-/co-treatment at a daily dose of 0.072 to 0.124 g/kg for 30 days protected against isoproterenol (ISO)-induced chronic myocardial damage in rats in a dose-dependent manner, with the extent of protection, as assessed by plasma cardiac troponin I level, being up to 76%. The cardioprotection afforded by HECP was associated with the enhancement of myocardial mitochondrial antioxidant status, amelioration of plasma parameters on cardiac dysfunction and hypertrophy, as well as an increase in myocardial endothelial nitric oxide synthase activity. Myocardial apoptotic and anti-apoptotic parameters were suppressed and stimulated, respectively. The cardioprotection afforded by HECP was accompanied by an increase in exercise capacity, an indirect functional index of the myocardium, in ISO-challenged rats. In conclusion, HECP may offer a promising prospect in preventing chronic heart failure in human subjects.

Antioxidant and Immunopotentiating Effects of <i>Cordyceps </i>Mycelium Extract, Chicken Essence, and Their Combination in Experimental Models

Cordyceps mycelium extract (Cs-4), Chicken Essence (CE), and their combination were investigated for antioxidant and immunomodulatory activities in mouse models. Long-term treatment with Cs-4 or CE at equivalent human doses improved antioxidant status in various tissues, as evidenced by the enhancement of mitochondrial glutathione redox status in the brain, liver, heart, and kidney of mice. Cs-4 or CE treatment also produced an immunomodulatory action, as indicated by the potentiation of Concanavalin A-/lipopolysaccharide-induced proliferation of mouse splenocytes ex vivo. While doubling of the equivalent human doses of Cs-4 and CE did not further enhance their antioxidant or immunopotentiating effects, the combined treatment with Cs-4 and CE at their respective equivalent human doses produced an additive effect, with the extents of stimulation being larger than those produced by Cs-4 or CE alone. The results have demonstrated for the first time that the combined use of Cs-4 and CE can produce an additive effect on both antioxidation and immunopotentiation that cannot otherwise be achieved by increasing the equivalent human doses of Cs-4 or CE alone.

Long-Term Treatment with an Herbal Formula MCC Ameliorates Obesity-Associated Metabolic Dysfunction in High Fat Diet-Induced Obese Mice: A Comparative Study among MCC and Various Combinations of Its Constituents

Obesity has been found to be associated with increased incidence of various metabolic disorders. Anti-obesity interventions are therefore urgently needed. An earlier study has demonstrated that treatment with an herbal formula MCC, which comprises the fruit of Momordica charantia (MC), the pericarpium of Citri reticulate (CR) and L-carnitine (CA), reduced the weight gain in high fat diet (HFD)-fed mice. In the present study, we investigated the effect of long-term treatment with MCC (6 g/kg/day × 40 doses) and various combinations of its constituents in HFD-fed female ICR mice. Body weight change was monitored during the course of the experiment. Total and differential adiposity, plasma lipid contents, metabolic enzyme activities and mitochondrial coupling efficiency in skeletal muscle were measured. Glucose homeostasis was also assessed. Results showed that HFD increased the body weight, total and differential adiposity, and plasma lipid contents as well as impaired metabolic status in skeletal muscle and glucose homeostasis. MCC and all combinations of its constituents reduced the weight gain in HFD-fed mice, which was accompanied with an improvement on glucose homeostasis. While MC, CA and CR independently suppressed the HFD-induced weight gain in mice, MC seems to be the most effective in weight reduction, all of which correlated with the induction of mitochondrial uncoupling in skeletal muscle. Only CA and CR, but not MC, significantly reduced the total adiposity and visceral adiposity as well as plasma cholesterol level. However, the two component combinations, MC + CR and MC + CA, decreased the degree of visceral adiposity and plasma cholesterol level, respectively. MCC treatment at 1.5 g/kg (but not a higher dose of 6 g/kg) suppressed visceral adiposity and induced mitochondrial uncoupling in skeletal muscle in HFD-fed mice. The finding suggests that MCC may offer a promising prospect for ameliorating the diet-induced obesity and metabolic disorders in humans.

Immunopotentiating Activity of Dendrobium Species in Mouse Splenocytes

This study aimed to explore a pharmacological activity marker for quality assurance of Dendrobium species. The immunopotentiating activity in aqueous extracts prepared from four Dendrobium species, including D. officinalis, was assessed by an in vitro assay of concanavalin A (Con A)-stimulated proliferation of mouse splenocytes. Four samples of commercially available Dendrobii Caulis were also analyzed for comparison. The results indicated that the aqueous extract of D. officinalis produced immunopotentiating action, as evidenced by the increase in Con A-stimulated proliferation of mouse splenocytes, with the extent of stimulation being more prominent than those of other tested Dendrobium species and Dendrobii Caulis samples. In conclusion, an in vitro immunopotentiation assay may be used for assessing the pharmacological activity of Dendrobium species. The finding that D. officinalis produced a more potent immunopotentiating action is consistent with its 'yin-nourishing' action in Chinese medicine, which is more effective than other Dendrobium species in clinical use.

Acute and Long-Term Treatments with an Herbal Formula V-Vital Capsule Increase Exercise Endurance Capacity in Weight-Loaded Swimming Mice

Fatigue is a self-limiting response arising from physical and/or mental weariness, with a consequent personal and economic morbidity on work performance and social relationships. Anti-fatigue intervention is therefore urgently sought. “Qi-invigorating” Chinese tonic herbs, which can improve the energy status in the body according to the theory of traditional Chinese medicine, may produce beneficial effects in fatigue individuals. The herbal formula V-Vital capsule (VVC), which comprises 3 “Qi-invigorating” herbs, namely the root of Rhodiola rosea, Eleutherococcus senticosus and Panax quinquefolium, may produce anti-fatigue effect. In the present study, we investigated the effect of acute/long-term VVC treatment (acute: 0.75, 0.2 and 3.75 kg/day × 1 dose;long-term: 0.075 and 0.25 g/kg/day × 14 doses) on weight-loaded swimming female ICR mice. The weight-loaded swimming time until exhaustion, indicative of exercise endurance capacity, was recorded. Plasma levels of glucose, non-esterified fatty acid (NEFA), lactate and reactive oxygen metabolites (ROM) were measured in the exhausted mice. Glycogen levels in skeletal muscle and liver tissues were also measured. Mitochondrial function status [such as adenine nucleotide translocase (ANT) activity and coupling efficiency] was assayed. Results showed that acute VVC treatment increased the exercise endurance capacity in weight-loaded swimming mice. The ability of acute VVC treatment to enhance the exercise endurance was associated with increases in plasma glucose levels as well as glycogen levels in skeletal muscles and liver tissues, presumably due to the utilization of plasma lactate for gluconeogenesis and/or glycogen synthesis in the liver. While acute VVC treatment reduced the plasma ROM level in weight-loaded swimming mice, it increased the ANT activity. In this regard, the enhancement in exercise endurance afforded by acute VVC treatment might be due to an increase in the glucose supply to the skeletal muscle, the amelioration of systemic oxidative stress and the improvement in mitochondrial function of skeletal muscle. Consistent with the results obtained in acute VVC treatment experiment, the long-term VVC treatment enhances the exercise endurance in weight-loaded swimming mice. The ensemble of results suggests that VVC may offer a promising prospect for enhancing the exercise endurance and alleviating fatigue in humans.

Long-Term Treatment with an Herbal Formula MCC Reduces the Weight Gain in High Fat Diet-Induced Obese Mice

Obesity is a risk factor for metabolic disorders, with its prevalence being increased in the world over the past several decades. Therapeutical interventions for obesity are thus urgently needed. In the present study, we investigated the effect of long-term treatment (0.51 and 5.1 g/kg/day, 5 days per week for a total of 40 doses) with an herbal formula MCC [which comprises the fruit of Momordica charantia (MC), the pericarpium of Citri reticulata and L-carnitine] in normal diet (ND) and high fat diet (HFD)-fed female ICR mice. Body weight change was monitored during the course of the experiment. Fat pad indices, plasma glucose and lipid contents, as well as metabolic enzyme activities and mitochondrial coupling efficiency in skeletal muscle were measured at 24 hours after the last dosing. Results showed that HFD increased the body weight, fat pad indices, plasma glucose and lipid contents as well as β-hydroxyacyl-Co A dehydrogenase (β-HAD) and carnitine palmitoyl CoA transferase (CPT) activities in skeletal muscle. However, the phosphofructokinase (PFK) activity was decreased in skeletal muscle. MCC treatment reduced the HFD-induced increases in body weight, fat pad indices and plasma lipid contents. MCC treatment only partially reversed the HFD-induced changes in β-HAD and CPT activities, but did not restore the HFD-induced decrease in PFK activity. MCC did not alter the plasma glucose level and mitochondrial coupling efficiency in skeletal muscle of ND and HFD-fed mice. Since MCC formula did not increase activities of energy metabolic enzymes or induce mitochondrial uncoupling, the weight loss effect of MCC is likely related to the reduction of intestinal lipid absorption in HFD-fed mice.