Thai traditional medicine as a source for cancer prevention: from local concepts to the discovery of potential chemopreventive extracts

Cancer chemoprevention aims to prevent, delay, or reverse carcinogenesis. Thai Traditional Medicine (TTM) could be a source for cancer chemopreventive agents and – more broadly –could play a role in cancer prevention. Using an ethnopharmacology approach this thesis aims to understand the pharmacological basis of some of these botanical drugs and to discover new extracts which could be useful in cancer prevention. Interviews with 33 TTM practitioners revealed the five characteristics of cancer in TTM (mareng), which is described as an accumulation of waste, chronic inflammation, chronic illnesses (krasai), bad condition of body fluids (‘luead’ and ‘namlueang’), and imbalance of dhātu si. Further analysis of preventive methods led to the five strategies for preventing mareng. To link TTM actions to pharmacology, we proposed that three strategies, removal of waste, liver protection, and prevention from krasai, can be linked to the antioxidant system. After screening of fifty-two extracts, fifteen exhibited protective effect in a liver cancer cell line. Among them, ethanol extracts of Thunbergia laurifolia leaves (TLe) and Senegalia rugata leaves (SR1e) exhibited the most potent activities in the induction of NQO1 enzyme and glutathione. Upregulation of antioxidant genes and radical scavenging were among their protective mechanisms. While TLe induced NQO1 expression, SR1e upregulated the expression of Nrf2. Both extracts did not induce CYP1A1 expression nor reduce cell viability of primary rat hepatocytes which provided preliminary safety profile. Using HPLC-HRMS-SPE-ttNMR, we could identify some active constituents in the extracts. This is the first report analysing how cancer is perceived in TTM, what prevention strategies are used, linking this to pharmacological models, and on chemopreventive properties of TLe and SR1e and some of their constituents. The evidence supports the potential use of these medicinal plants in cancer prevention. Future work should be performed with more TTM practitioners and use in vivo models

Effect of Moringa oleifera Leaf Capsules on Glycemic Control in Therapy-Naïve Type 2 Diabetes Patients: A Randomized Placebo Controlled Study

Background. Studies showed effects of Moringa oleifera (MO) on lowering blood sugar levels in animal and diabetes patients. The aims of this study were to determine the effect of MO leaf capsules on glucose control in therapy-naïve type 2 diabetes mellitus (T2DM) and to evaluate its safety. Method. This was a prospective randomized placebo controlled study. Therapy-naïve T2DM was randomly assigned to receive either 8 grams per day of MO leaf capsules (MO leaf group) or placebo for 4 weeks. Clinical and laboratory characteristics were recorded at screening and at the end of 4-week study. 9-point plasma glucose was obtained before and every week during the study. Results. Thirty-two T2DM patients were enrolled. The mean age was 55 years and the mean HbA1C was 7.0%. There was no significant difference in FPG and HbA1C between groups. MO leaf group had SBP reduction by 5 mmHg as compared to baseline but this difference had no statistical significance. There were no adverse effects of MO leaf. Conclusions. Moringa oleifera leaf had no effect on glycemic control and no adverse effects in T2DM. Interestingly, this study demonstrated that MO leaf had a tendency on blood pressure reduction in T2DM, and this result needs further investigation

The Effect of Thai Herbal Ha-Rak Formula (HRF) on LPS-Induced Systemic Inflammation in Wistar Rats

Objective: To study effects of Thai herbal Ha-rak formula (HRF) on lipopolysaccharide (LPS)-induced systemic inflammation in rats. Methods: Male Wistar rats (190-250 g) were orally treated with HRF for 14 days before they were induced with LPS (6 mg/kg, i.v.). The markers of organ injury/dysfunction and pro-inflammatory cytokines were measured at 6 hours after LPS administration. Results: LPS administration can significantly increase all markers. Intragastric administration of 5 mg/kg indomethacin, the positive control, significantly reduced plasma urea, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), creatinine kinase (CK), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6. HRF trends to attenuate the plasma AST, ALT, CK, TNF-a, and IL-1β, although these effects were not statistically significant. Moreover, all doses of HRF did not increase plasma urea, creatinine, AST, ALT, CK, and lipase, when compared to sham. Conclusion: HRF trends to protect against endotoxemia-induced organ injuries and pro-inflammatory cytokines. Furthermore, rats that received HRF did not show organ injuries

The safety of Homnawakod herbal formula containing <it>Aristolochia tagala</it> Cham. in Wistar rats

<p>Abstract</p> <p>Background</p> <p>A dried root of <it>Aristolochia tagala</it> Cham. (ATC) is often used in Thai traditional medicine as an antipyretic, anti-inflammatory agent, muscle relaxant, appetite-enhancing agent, and analeptic. Homnawakod, an important herbal recipe, originally contains ATC in its formula, however, some <it>Aristolochia</it> species have been reported to cause nephrotoxicity due to aristolochic acid (AA) and its derivatives, resulting in ATC removal from all formulae. Therefore, this study investigates the chemical profiles of ATC, the original (HNK+ATC) and the present Homnawakod Ayurved Siriraj Herbal Formulary™ (HNK), and investigates whether they could cause nephrotoxicity or aggravate LPS-induced organ injuries <it>in vivo</it>.</p> <p>Methods</p> <p>HPLC and LC/MS were used for chemical profile study. Male Wistar rats were randomly divided into groups in which the rats were intragastrically administered distilled water (2 groups), ATC (10 or 30 mg/kg), HNK+ATC (540 or 1,620 mg/kg), or HNK (1,590 mg/kg) for 21 days. A positive control group was administered with single dose 100 mg/kg standard AA-I intragastrically at day 1. Serum creatinine and urea were measured at baseline and at 7, 14 and 21 days of the treatment. On day 22, a model of lipopolysaccharide (LPS)-induced endotoxemia was used. One-way and two-way analyses of variance were performed and a <it>P</it> value of less than 0.05 was considered to be significant.</p> <p>Results</p> <p>The similarity of the HPLC chromatograms of HNK+ATC and HNK could suggest that the qualities of both formulae are nearly the same in terms of chemical profile. The amount of AA-I found in ATC is 0.24%w/w. All experimental groups exhibited similar levels of serum urea at baseline and 7 and 14 days of the treatment. At 21 days, rats received AA exhibited a significant increase in serum urea, whereas the others did not exhibit such toxicity. On day 22, there were no significant changes in LPS-induced renal and liver dysfunction, or LPS-induced mean arterial pressure (MAP) reduction upon administration of ATC, HNK+ATC, HNK or AA-I.</p> <p>Conclusions</p> <p>These results suggest that ATC, HNK+ATC or HNK, at the animal dose equivalent to that used in human, do not cause the acute nephrotoxicity in rats and do not aggravate LPS-induced organ injuries even further.</p