Vitamin C alleviates rheumatoid arthritis by modulating gut microbiota balance.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and symmetric in-flammation. Our previous research revealed an imbalance in the gut flora of RA patients and showed that certain gut microbiota can accelerate RA progression by enhancing vitamin C degradation. However, it is unclear whether vitamin C supplementation could improve the gut microbiota to prevent the development of arthritis by interfering with the gut-joint axis. In this work, we aimed to evaluate the effects of vitamin C in regulating the gut microbiota and to elucidate its potential role in the onset and progression of RA in a mouse model, thus providing a basis for the development of new intervention strategies and treatments for RA. In this study, collagen-induced arthritis (CIA) mouse models, biochemical, histological and 16S rRNA microbiological methods were used to investigate the role and possible mechanism of vitamin C in rheumatoid arthritis. The results showed that treatment of CIA mice with vitamin C effectively rescued the gut mi-crobiota imbalance and suppressed the inflammatory response associated with RA, and effectively alleviated arthritis symptoms in mice in which levels of the pro-inflammatory cytokines IL-6 and TNF-α were specifi-cally reduced. In conclusion, our results demonstrate the potential of vitamin C as a potential therapeutic choice for RA.

Ultra-weak photon emission as a potential tool for evaluating the therapeutic effect of traditional Chinese medicine in patients with type 2 diabetes.

Background: Traditional Chinese medicine (TCM) has been used to prevent and treat type 2 diabetes (T2DM) for thousands of years. The holistic view of TCM and the "multitarget" characteristics of Chinese medicine have unique advantages in the prevention and treatment of T2DM. TCM syndrome differentiation and treatment are effective for T2DM; however, currently, the therapeutic effect of TCM is generally evaluated by asking for patients' subjective feelings, or by checking the changes in relevant indicators. The main problems are that the patient's descriptions are unclear and subjective, and although the self-reported symptoms may have improved significantly, the relevant indicators are sometimes not obvious, which cannot truly reflect the therapeutic effect of TCM. Therefore, it is urgent to develop a novel, sensitive, and noninvasive method to quantitatively evaluate the therapeutic effect of TCM. Methods: In this study, ultra-weak photon emission (UPE) was measured at four sites of hands of T2DM patients with Qi-Yin deficiency before treatment and after 1 and 2 weeks of treatment with TCM. The UPE intensity and spectral distribution were calculated and analyzed using the results measured at these four sites. Spearman's correlation coefficient was used to quantify the correlation between the UPE parameters and the syndrome scores of TCM. Results: The UPE intensity of T2DM patients with Qi-Yin deficiency decreased gradually with the course of the treatment and was significantly lower than that before the treatment. The ratio of photon counts between the wavelength ranges of 495-550 nm and 550-610 nm after the treatment was higher than that before the treatment and negatively correlated with the corresponding syndrome scores so that the degree of symptoms improvement could be characterized by the ratio (495-550 nm/550-610 nm). Conclusions: The therapeutic effect of TCM in T2DM patients with Qi-Yin deficiency can be shown at the level of UPE. UPE is a potential and noninvasive tool for evaluating the therapeutic effect of TCM in patients with T2DM.

Corrigendum: A biophoton method for identifying the quality states of fresh Chinese herbs.

[This corrects the article DOI: 10.3389/fphar.2023.1140117.].

A biophoton method for identifying the quality states of fresh Chinese herbs.

Introduction: The quality of Chinese herbs is the basis for ensuring their safety and efficacy. However, the quality evaluation system is imperfect. In particular, there is a lack of quality evaluation methods for fresh Chinese herbs during growth. The biophoton is a common phenomenon and provides complete information about the interior of the living system, which is consistent with the holistic concept of traditional Chinese medicine. Therefore, we aim to correlate the biophoton characteristics with the quality states to find the biophoton parameters that can characterize the quality states of fresh Chinese herbs. Methods: The biophoton characteristics of motherwort and safflower were measured and characterized by the counts per second (CPS) in the steady state and the initial intensity (I0) and coherent time (T) of delayed luminescence. The active ingredient content was measured by ultra-high-performance liquid chromatography (UPLC). The pigment content of motherwort leaves was measured by UV spectrophotometry. The t-test and correlation analysis were performed on the experimental results. Results: The CPS and I0 of motherwort and I0 of safflower showed a significant downward trend during the growth process, and their active ingredient content showed a trend that increased and then decreased. The CPS, I0, and the content of active ingredients and pigments in a healthy state were significantly higher than those in a poor state, while T showed the opposite results. The CPS and I0 were all significantly and positively correlated with the content of active ingredients and pigments, while the T of motherwort showed the opposite results. Conclusion: It is feasible to identify the quality states of fresh Chinese herbs by using their biophoton characteristics. Both CPS and I0 have better correlations with the quality states and can be considered characteristic parameters of the quality of fresh Chinese herbs.

The application and trend of ultra-weak photon emission in biology and medicine.

Ultra-weak bioluminescence, also known as ultra-weak photon emission (UPE), is one of the functional characteristics of biological organisms, characterized by specialized, low-energy level luminescence. Researchers have extensively studied UPE for decades, and the mechanisms by which UPE is generated and its properties have been extensively investigated. However, there has been a gradual shift in research focus on UPE in recent years toward exploring its application value. To better understand the application and trend of UPE in biology and medicine, we have conducted a review of relevant articles in recent years. Among the several topics covered in this review is UPE research in biology and medicine (including traditional Chinese medicine), primarily focused on UPE as a promising non-invasive tool for diagnosis and oxidative metabolism monitoring as well as a potential tool for traditional Chinese medicine research.

The modulation of gut microbiota by herbal medicine to alleviate diabetic kidney disease - A review.

The treatment of diabetic kidney disease (DKD) has been the key concern of the medical community. Herbal medicine has been reported to alleviate intestinal dysbiosis, promote the excretion of toxic metabolites, and reduce the secretion of uremic toxins. However, the current understanding of the modulation of the gut microbiota by herbal medicine to delay the progression of DKD is still insufficient. Consequently, we reviewed the knowledge based on peer-reviewed English-language journals regarding regulating gut microbiota by herbal medicines in DKD. It was found that herbal medicine or their natural extracts may have the following effects: modulating the composition of intestinal flora, particularly Akkermansia, Lactobacillus, and Bacteroidetes, as well as adjusting the F/B ratio; increasing the production of SCFAs and restoring the intestinal barrier; reducing the concentration of uremic toxins (p-cresol sulfate, indole sulfate, TMAO); inhibiting inflammation and oxidative stress.

Analysis of the network pharmacology and the structure-activity relationship of glycyrrhizic acid and glycyrrhetinic acid.

Licorice, a herbal product derived from the root of Glycyrrhiza species, has been used as a sweetening agent and traditional herbal medicine for hundreds of years. Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) are the most important active ingredients in licorice. Both GL and GA have pharmacological effects against tumors, inflammation, viral infection, liver diseases, neurological diseases, and metabolic diseases. However, they also exhibit differences. KEGG analysis indicated that licorice is involved in neuroactive ligand‒receptor interactions, while 18ß-GA is mostly involved in arrhythmogenic right ventricular cardiomyopathy. In this article, we comprehensively review the therapeutic potential of GL and GA by focusing on their pharmacological effects and working mechanisms. We systemically examine the structure-activity relationship of GL, GA and their isomers. Based on the various pharmacological activities of GL, GA and their isomers, we propose further development of structural derivatives of GA after chemical structure modification, with less cytotoxicity but higher targeting specificity. More research is needed on the clinical applications of licorice and its active ingredients.

Bidirectional regulatory effects of Cordyceps on arrhythmia: Clinical evaluations and network pharmacology.

Background: Cordyceps is a precious Chinese herbal medicine with rich bio-active ingredients and is used for regulating arrhythmia alongside routine treatments. However, the efficacy and potential mechanisms of Cordyceps on patients with arrhythmia remain unclear. Methods: Randomized controlled trials of bradycardia treatment with Cordyceps were retrieved from diverse databases and available data. Dichotomous variables were expressed as a risk ratio (RR) with a 95% confidence interval (CI). Continuous variables were expressed as a standardized mean difference (SMD) with a 95% CI. Network pharmacology was used to identify potential targets of Cordyceps for arrhythmia. Metascape was used for gene ontology (GO) and genome (KEGG) pathway enrichment analysis. Results: Nineteen trials included 1,805 patients with arrhythmia, of whom 918 were treated with Ningxinbao capsule plus routine drugs, and, as a control, 887 were treated with only routine drugs. Six trials reported on bradycardia and the other 13 on tachycardia. Treatment with Cordyceps significantly improved the total efficacy rate in both bradycardia (RR = 1.24; 95% CI, 1.15 to 1.35; Pz <0.00001) and tachycardia (RR = 1.27; 95% CI, 1.17 to 1.39; Pz <0.00001). Cordyceps also had beneficial secondary outcomes. No serious adverse events occurred in patients treated with Cordyceps. The results of KEGG pathway enrichment analysis were mainly connected to adrenergic signaling in cardiomyocytes and the PI3K-Akt signaling pathway. IL6, TNF, TP53, CASP3, CTNNB1, EGF, and NOS3 might be key targets for Cordyceps in the treatment of arrhythmia. Conclusion: This study confirmed that Cordyceps has a certain positive effect on the treatment of arrhythmia and that its main mechanism may be through the regulation of adrenergic signaling in cardiomyocytes and the PI3K-Akt signaling pathway.

K Value: An Indicator that can Characterize the Cold and Hot Properties of Traditional Chinese Medicines.

Aims: The cold and hot properties of Chinese medicines are an important concept to represent the function of drugs, and are also a unique classification method of traditional Chinese medicine (TCM). The method reflects an herb's therapeutic properties and guides reasonable clinical prescription. However, the present key problem is the lack of an objective and quantitative evaluation index for the cold and hot properties of Chinese herbs. Delayed luminescence (DL) is the long-term afterglow of biological systems after illumination with light, which can reflect differences in herbal materials prepared under different conditions. We aim to use S. obliquus as an indicator organism to characterize the differences between the cold and hot properties of Chinese herbs. Methods: Scenedesmus obliquus (S. obliquus) was used as an indicator organism to characterize the differences between the cold and hot properties of Chinese herbs. The decoction solution of different properties of Chinese herbs was added to S. obliquus culture medium; then, the delayed luminescence (DL) of S. obliquus after the addition of decoctions of different properties of Chinese herbs was measured to obtain information on the effect of different properties of Chinese herbs on S. obliquus. Many DL parameters were calculated, and ROC curve analysis was applied with the aim of finding a suitable parameter that can characterize the differences in cold and hot properties of Chinese herbs. Results: Our results show that the K value is a sensitive parameter that can reflect the differences of cold and hot properties of Chinese herbs, thus providing new insights into the cold and hot properties of Chinese herbs. Conclusions: DL measurement of S. obliquus after addition of different properties of Chinese herbs could be a novel and promising method to study the cold and hot properties of Chinese herbs.

A Network Pharmacology Approach for Uncovering the Osteogenic Mechanisms of Psoralea corylifolia Linn.

BACKGROUND AND AIM: Psoralea corylifolia Linn (PCL) is an herb that is commonly used for alleviating osteoporosis and vitiligo. Although accumulating evidence has demonstrated the antiosteoporotic effect of PCL, the identities of the osteogenic compounds in PCL and their functional targets remain elusive. To investigate the osteogenic ingredients in PCL and their functional mechanisms, network pharmacology analysis was performed on the targets of PCL and osteogenesis. METHODS: The active components of PCL were screened by literature review. The potential protein targets of the active PCL components were predicted with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Search Tool for Interactions of Chemicals (STITCH), SwissTargetPrediction, and PubChem. The target networks related to PCL and osteogenic differentiation were constructed by using Cytoscape. MC3T3-E1 cells were used to verify the targets. RESULTS: Twenty-three active components of PCL and 162 potential target proteins were identified. Further analysis reduced the number of potential target proteins to 71. Of the 23 components, bavachalcone, psoralen, bavachinin, neobavaisoflavone, methoxsalen, psoradin, bakuchiol, and angelicin may be the main active components of PCL that promote bone formation. PPARγ and aryl hydrocarbon receptor (AhR) were verified as targets of PCL in MC3T3-E1 cells, and the western blot and immunofluorescence staining results showed that compared to the control, PCL reduced the expression of these targets. CONCLUSIONS: The active components of PCL and the mechanisms by which they promoted osteogenic differentiation were successfully identified using network pharmacology.

Icariin Promotes the Osteogenic Action of BMP2 by Activating the cAMP Signaling Pathway.

Icariin (ICA) is the main active flavonoid glucoside from herbs of the genus Epimedium; in traditional Chinese medicine, these herbs have long been prescribed for the treatment of bone fractures and osteoporosis. Several studies have shown that treatment with ICA can increase osteogenic differentiation and reduce bone loss in vivo and in vitro. However, the definite signaling pathway of this osteogenic effect remains unclear. In this study, we selected bone morphogenetic protein 2 (BMP2)-induced osteoblastic differentiation of multipotent mesenchymal progenitor C2C12 cells as a model of osteoblast differentiation. We investigated the effects of ICA on C2C12 cells osteogenic differentiation and the underlying molecular mechanisms. We found that ICA could enhance BMP2-mediated osteoblastic differentiation of C2C12 cells in a dose-dependent manner. Treatment with ICA activated the cAMP/PKA/CREB signaling axis in a time-dependent manner. Blocking cAMP signaling using the PKA selective inhibitor H89 significantly inhibited the stimulatory effect of ICA on osteogenesis. Therefore, the osteoinductive potential and the low cost of ICA indicate that it is a promising alternative treatment or promoter for enhancing the therapeutic effects of BMP2.

Characterization of the hot and cold medicinal properties of traditional Chinese herbs by spontaneous photon emission ratio of mice.

ETHNOPHARMACOLOGICAL RELEVANCE: One important therapeutic characteristic of traditional Chinese medicine (TCM) for its properly-guided clinical prescription is considering the cold and hot medicinal properties of traditional Chinese herbs. According to the TCM theory, the hot and cold medicinal properties are defined by the general responses of a human body to a given herbal medicine. This definition is subjective and ambiguous which attenuates the modernization of TCM. Biological spontaneous photon emission (SE) is a normal phenomenon reflecting the transition of the quantum state of molecules inside an organism. The alteration of its level can indicate the changes of many aspects of the organism including metabolism. Thus, we can exploit this feature to develop a novel and scientific approach to quantitively and objectively characterize the hot and cold medicinal properties of traditional Chinese herbs. OBJECTIVE: To determine whether SE can be used to characterize the hot and cold medicinal properties of traditional Chinese herbs, this study took advantage of the ultra-weak luminescence detection technology to examine the effects of traditional Chinese herbs with hot or cold medicinal property to the level of SE in mice. MATERIALS AND METHODS: Mice were intragastrically administered with twenty traditional Chinese herbs harboring cold or hot property for ten consecutive days respectively. During the course of treatment, SE intensity of the abdomen and the back of each individual mouse were measured and recorded. At the end of the treatment, the total antioxidant capacity, superoxide dismutase activity, Na+-K+-ATPase activity and Ca2+-Mg2+-ATPase activity in the liver of all mice were examined. RESULTS: Ratio between the SE intensity of the abdomen and back of mice (defined as SE ratio) was able to distinguish the cold and hot medicinal properties of traditional Chinese herbs. Mice treated with hot herbs and cold herbs have higher and lower SE ratios respectively compared with control mice. Furthermore, levels of selected biochemical indexes in the liver were correlated with most of the SE ratio changes induced by herbal treatment. CONCLUSIONS: We have developed a novel and promising approach to quantitatively investigate herbal properties and we propose that SE ratio defined in this study can serve as a sensitive parameter to characterize the cold and hot medicinal properties of traditional Chinese herbs.

A Bridge of Light: Toward Chinese and Western Medicine Perspectives Through Ultraweak Photon Emissions.

The gap between Western medicine and traditional Chinese medicine (CM) is closely related to the diversity in culture, philosophy, and scientific developments. Although numerous studies have evaluated the efficacy of acupuncture, the gap in explanatory disease models has not been bridged so far. Developments in research of ultraweak photon emission (UPE) and organized dynamics of metabolism and its relationship with technological advances in metabolomics have created the conditions to bring the basics of the medicines of the West and East together which might open the avenue for a scientific dialogue. The paper discusses (1) the UPE in relation to Qi energy, meridians and acupuncture points in CM, (2) the biochemical explanation of photon emission of living systems in Western biomedicine, and (3) the progress in research on the large-scale organization and dynamics of the metabolic network including photon metabolism.

Epidemiology, diagnosis, and treatment of Wilson's disease.

Wilson's disease (WD) is an autosomal recessive disease caused by a mutation of the ATP7B gene, resulting in abnormal copper metabolism. The major clinical features of WD include liver disease, neurological disorders, K-F rings, and osteoporosis. The prevalence of WD in China is higher than that in Western countries. Early diagnosis and lifelong treatment will lead to better outcomes. Drugs such as sodium dimercaptosuccinate (Na-DMPS), Zn, and Gandou Decoction can be used to treat WD. Some studies have shown that the combination of traditional Chinese medicine and Western medicine is the best approach to treating WD. In order to identify better treatments, this article describes the specific clinical symptoms of Wilson's disease, its diagnosis, and treatment options.

Application of Spontaneous Photon Emission in the Growth Ages and Varieties Screening of Fresh Chinese Herbal Medicines.

Ultraweak photon emission emitted by all living organisms has been confirmed to be a noninvasive indicator for their physiological and pathological characteristics. In this study, we investigated the characteristics of spontaneous photon emission (SPE) and the contents of specific active compounds of roots and flowers buds of several fresh Chinese herbal medicines (natural medicines) with different growth ages and varieties. The results revealed that the contents of specific active compounds from same species herbs with different growth ages and varieties were significantly different, and this difference could be reflected by their SPE. Because the contents of specific bioactive constituents in Chinese herbs are closely related to their quality and curative effect, the SPE measurement technique may contribute to the quality control of Chinese herbal medicine in the future.

Spectral Analysis of Chinese Medicinal Herbs Based on Delayed Luminescence.

Traditional Chinese medicine (TCM) plays a critical role in healthcare; however, it lacks scientific evidence to support the multidimensional therapeutic effects. These effects are based on experience, and, to date, there is no advanced tool to evaluate these experience based effects. In the current study, Chinese herbal materials classified with different cold and heat therapeutic properties, based on Chinese medicine principles, were investigated using spectral distribution, as well as the decay probability distribution based on delayed luminescence (DL). A detection system based on ultraweak biophoton emission was developed to determine the DL decay kinetics of the cold and heat properties of Chinese herbal materials. We constructed a mathematical model to fit the experimental data and characterize the properties of Chinese medicinal herbs with different parameters. The results demonstrated that this method has good reproducibility. Moreover, there is a significant difference (p < 0.05) in the spectral distribution and the decay probability distribution of Chinese herbal materials with cold and heat properties. This approach takes advantage of the comprehensive nature of DL compared with more reductionist approaches and is more consistent with TCM principles, in which the core comprises holistic views.

Classification of Chinese herbs based on the cluster analysis of delayed luminescence.

Traditional Chinese material medica are an important component of the Chinese pharmacopeia. According to the traditional Chinese medicinal concept, Chinese herbal medicines are classified into different categories based on their therapeutic effects, however, the bioactive principles cannot be solely explained by chemical analysis. The aim of this study is to classify different Chinese herbs based on their therapeutic effects by using delayed luminescence (DL). The DL of 56 Chinese herbs was measured using an ultra-sensitive luminescence detection system. The different DL parameters were used to classify Chinese herbs according to a hierarchical cluster analysis. The samples were divided into two groups based on their DL kinetic parameters. Interestingly, the DL classification results were quite consistent with classification according to the Chinese medicinal concepts of 'cold' and 'heat' properties. In this paper, we show for the first time that by using DL technology, it is possible to classify Chinese herbs according to the Chinese medicinal concept and it may even be possible to predict their therapeutic properties.

Correlation between the different therapeutic properties of Chinese medicinal herbs and delayed luminescence.

In the practice and principle of Chinese medicine, herbal materials are classified according to their therapeutic properties. 'Cold' and 'heat' are the most important classes of Chinese medicinal herbs according to the theory of traditional Chinese medicine (TCM). In this work, delayed luminescence (DL) was measured for different samples of Chinese medicinal herbs using a sensitive photon multiplier detection system. A comparison of DL parameters, including mean intensity and statistic entropy, was undertaken to discriminate between the 'cold' and 'heat' properties of Chinese medicinal herbs. The results suggest that there are significant differences in mean intensity and statistic entropy and using this method combined with statistical analysis may provide novel parameters for the characterization of Chinese medicinal herbs in relation to their energetic properties.

Review and analysis on the meridian research of China over the past sixty years.

The meridian research situation and various meridian hypotheses of China in the past sixty years between 1950 and 2013 are summarized in the paper; possible existed problems in the process of current meridian research are analyzed. Based on previous research results, we proposed that the essence of meridian can not be explained by the reductive analysis method, meridian research should be carried out under the guidance of overall concept of Chinese medicine theory. In this paper, combined with coherence theory of biophoton, we put forward the quantum interference hypothesis of meridian, which provides a possible research idea for meridian study.