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.

Inter-Organ Relationships among Gut, Lung and Skin beyond the Pathogenesis of Allergies: Relevance to the Zang-Fu Theory in Chinese Medicine

Research on allergy has recently uncovered an apparent co-occurrence of allergies in skin and the lungs, a phenomenon that has been coined “atopic march”. A positive correlation has been found between gut microbiota at birth and the development of asthma and skin eczema later in life. Chinese medicine has long described a functional relationship between the large intestine and the lungs, and between the lungs and skin. In this short article, we examined the evidence in support of these inter-organ physiological/pathological relationships. In addition to the clinical observation of the relationship between the composition of gut microbiota at birth and the development of asthma later in childhood, gut microorganisms have also been shown to exert a protective effect on bacteria-induced pneumonia in experimental animals. Genetic predisposition was also found to play an important role in the co-existence of certain diseases of lung and skin. Despite the fact that the mechanism(s) underlying the connection of immune systems between two organs (such as the large intestine and the lungs) is still not clearly understood, it is the first time to correlate the relationship among gut, lung and skin based on recent clinical studies in relation to the Zang-Fu Theory in Chinese medicine. Future investigation of the gut-lung and lung-skin axes in terms of physiological/pathological relationships may help to provide a greater understanding of the pathogenesis of allergies, possibly establishing relevance to the Zang-Fu Theory in Chinese medicine.

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.

Investigation of in Vitro and in Vivo Metabolism of Schisandrin B from Schisandrae Fructus by Liquid Chromatography Coupled Electrospray Ionization Tandem Mass Spectrometry

Schisandrin B (Sch B) is one of the active dibenzocyclooctadiene lignans found in the Schisandrae Fructus. Experimental studies have shown that Sch B possesses various pharmacological properties, including anti-cancer, neuroprotective and nephroprotective activities. However, no detailed information on its biotransformation was reported in the literature. Here, we investigated the in vitro and in vivo metabolism of Sch B by using ultra-performance liquid chromatography coupled with tandem mass spectrometry. In vitro study detected and identified one oxygenated metabolite. Four metabolites were detected and identified from the in vivo study. The results indicated that the metabolism of Sch B mainly involved the demethylation of methoxy groups, the opening of five-member ring and the glucuronidation of metabolites in rats. The metabolites were identified for the first time by MS/MS analyses.

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.

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.