Traditional Chinese herbs as chemical resource library for drug discovery of anti-infective and anti-inflammatory

Infection is a group of major diseases which are induced by invasions of bacterial, fungal, viral, and parasitic pathogens. Infective diseases are a significant cause of mortality and morbidity worldwide which caused 10.5 million people death in 2011, according to the statistics of World Health Organization (World Health Organization, 2014). Currently, antibiotics are major drugs for treatment of infections. However, we are facing the challenge of bacterial resistances that were caused by the use and abuse of antibiotics (Cars et al., 2008). Before the discovery of antibiotics in the 1950s, the main method for treating those diseases was to find healing methods from herbs. Since the antibiotic resistances emerged, the use of antimicrobial and other drugs derived from medical plants has been increasingly receptive again (Cowan, 1999).

More than 12,000 species of medicinal plants were used in China according to the third national survey on Chinese material resources (The China Medicinal Materials Co., 1994). The herbs have been used for treatment of diseases more than four thousand years and some herbs are still widely used in traditional medicine (Mahady, 2005). For example, the flower of Lonicera japonica, the root of Coptis chinensis and the aerial part of Artemisia annua were used for anti-infection and anti-inflammatory ( Woerdenbag et al., 1990, Schinella et al., 2002 and Shang et al., 2011). Chinese modern medicines were created based on these herbs, such as Reduning injection, Qinkailing injection and Shuanghuanglian oral liquid, which were widely used in treatment of common cold and influenza ( Wu et al., 2008 and Zhang et al., 2013). In-depth phytochemical investigation from herbs afforded enormous natural products which gave us a natural chemical library for drug discovery. In last 30 years, about 50 percent new chemical entities of FDA-approved drugs were discovered from natural products or derivatives, especially in antibacterial filed (Newman and Cragg, 2012). Moreover it was believed that natural products would still provide an unlimited opportunity for new drug leads discovery ( Cos et al., 2006).

Traditional Chinese herbs have been popularly used in health care and becoming more accepted worldwide. More and more compounds were isolated from herbs, which gave us an opportunity to use these herbs as a chemical resource library for drug discovery. In this study, we collected 1156 kinds of herbs and 22,172 traditional Chinese medicinal compounds (Tcmcs) to study the anti-infective and anti-inflammatory activities of traditional Chinese herbs.

Ding et al., (2014) constructed a phylogenetic tree to explore the distributions of anti-infective or anti-inflammatory herbs, and it showed that most of herb sources were distributed in plantae, especially in the family of Asteraceae. Moreover, herbs would have more common compounds if they had shorter evolutionary distance in the phylogenetic tree, indicating that we can find the alternative herbs by similarity.To evaluate the drug-likeness of Tcmcs, they explored the distributions of Tcmcs and drugs in molecular descriptors and chemical space. The Tcmcs and drugs had similar distributions in AlogP, rotatable bonds.

And Tcmcs shared a large overlap area with drugs in chemical space. Most of Tcmcs had good drug-likeness and it would provide a chance for leads discovery from Tcmcs.We also predicted the antibacterial, antiviral, antimalarial and anti-inflammatory potentials of herbs by using molecular dockings and the docking score weighted predictive models. The predictions obtained good specificity and sensitivity with the AUC values above 0.8, which were validated by publically available literatures. The optimal cutoff values of ROC curves were used to select most potential herbs. Finally, we obtained 389 kinds herbs, and most of them were classified in Asteraceae, Lamiaceae and Fabaceae. The three plant families would be the most potential herb resources for treatment of infection and inflammation.

Source: Ding Wx, Gu Jy, Cao L, et al. Journal of Ethnopharmacology. Volume 155, Issue 1, 8 August 2014, Pages 589–598



Bai Hua She She Cao, Herba Oldenlandia

Oral indigestion of this herb was found to have a dose-dependent effect to enhance macrophage function in vitro and inhibit tumour growth in vivo.
Ref.: Wong BY, Lau BH, Jia TY, Wan CP. Oldenlandia diffusa and Scutellaria barbata augment macrophage oxidative burst and inhibit tumour growth. ‘Cancer Biother Radiopharm' 1996 Feb; 11 (1):5-6

Dong Ling Cao, Herba Rabdosiae

Esophageal and cardiac cancer: In one study, 95 patients with middle-to-late stage esophageal and cardiac cancer were treated with preparations of this herb. Preparation I was made by mixing the herb with syrup (1:1 ratio); the treatment protocol was to give 20 to 30 ml three times daily for 2 to 3 months per course of treatment. Preparation II was made by incorporating 4.5 to 5 grams of the herb into pills three times daily for 2 to 3 months per course of treatment. Preparation III was made by mixing 75 to 100 mg of the active ingredient, Rubescensine A, in 500 ml of D5W; the treatment protocol was to infuse the preparation IV every other day until a total of 3000 to 3500 mg of compound had been given. The study concluded the rate of effectiveness was 26.7% for Preparation I, 27.6% for Preparation II and 31.8% for Preparation III.
Liver cancer: According to one study, 31 patients with primary liver cancer were treated successfully with preparations of this herb. Improved appetite and reduced pain were reported in 80% of the subjects. The survival rate after treatment was 29.6% after 6 months, 12% after one year and 10% after 2 years.
Ref.: Xian Dai Zhong Yao Li Xue (Contemporary Pharmacology of Chinese Herbs), 1997; 1468-1469; and He Nan Yi Xue Yuan Xue Bao (Journal of Henen University of Medicine) 1976; (5):22.

Ban Mao, Mylabris

Liver cancer: In one study, 300 patients were treated with cantharidin, the active ingredient in Ban Mao, and chemotherapy or radiotherapy. The protocol for cantharidin was 0.25 to 0.5 mg three times daily. The study reported and all-over rate of effectiveness of 65% based on symptomatic evaluation and the tumour size in the liver. In another study, 2 to 6 pills of the herb (each pill contained 0.25 mg of cantharidin, Bai Ji (Rhizoma Bletillae), aluminium hydroxide, and others) were given to 800 patients with liver cancer daily with 45 to 60% showing positive results. There were reductions of symptoms; decrease of tumour size and 12.7% of patients

Mu Dan Pi

Cortex Moutan Radicis
Class: Clear Heat
Subclass: Cool the Blood
Moves Blood.
Eliminates Blood accumulation.

The root bark of Paeonia moutan is a potential anticancer agent in human oral squamous cell carcinoma cells.
Li C, Yazawa K, Kondo S, Mukudai Y, Sato D, Kurihara Y, Kamatani T, Shintani S. Anticancer Res. 2012 Jul;32(7):2625-30.

Currently there is growing use of complementary and alternative anticancer medicines worldwide, and considerable interest in finding anticancer drugs among Chinese medicinal herbs. The aim of this study was to determine the antitumor activity of the root bark of Paeonia moutan (RBPM) in human squamous cell carcinoma (OSCC) cells. Cell lines derived from human oral squamous cell carcinoma (HSC2, 3, 4, SAS) were tested with different concentrations of RBPM (1-100 g/ml) using a series of in vitro assay systems. RBPM at a concentration of 100 g/ml inhibited monolayer and anchorage-independent growth, and interrupted coordinated migration. RBPM activated the phosphorylation of extracellular signal-regulated kinase (ERK) and serine/threonine kinase AKT in 30 min; then, at a later stage (after 6 hours) exhibited potent cytostatic, pro-apoptotic effects through the down-regulation of the expression of cyclin-dependent kinase 4 and its partner cyclin D1, and poly(ADP-ribose) polymerase cleavage. We found direct evidence that RBPM induces apoptotic cell death via DNA fragmentation. Taken together, the antitumor activity of RBPM was demonstrated through antiproliferative and apoptotic effects.

Antitumor effect of extracts from moutan cortex on DLD-1 human colon cancer cells in vitro.
Xing G, Zhang Z, Liu J, Hu H, Sugiura N. Mol Med Report. 2010 Jan-Feb;3(1):57-61. doi: 10.3892/mmr_00000218.

Moutan cortex, the root bark of Paeonia suffruticosa Andrews (Paeoniaceae), is a traditional Chinese medicine widely used for the treatment of various diseases. In the present study, we examined the antiproliferative effect and apoptosis-inducing activity of paeonol and the crude total glycosides (CTG) extracted from moutan cortex against DLD-1 human colon cancer cells in vitro. Cell viability was measured using the WST-8 assay. Apoptosis was detected by Hoechst 33258 fluorescence staining and flow cytometry. Paeonol and the CTG significantly reduced cell viability in a dose- and time-dependent manner. The induction of apoptosis in DLD-1 cells was characterized by morphological changes and an increased percentage of hypodiploid cells. After treatment for 48 h with paeonol (400 g/ml) or CTG (200 g/ml), the ratio of apoptotic cells reached 34.79 and 48.12%, respectively. The findings obtained indicate that paeonol and the CTG extracted from moutan cortex have a significant growth-inhibitory effect on human colon cancer cells. This effect may be related to the induction of apoptosis.