Integrative biology for integrative medicine: A complete approach.

BACKGROUND: India's AYUSH systems of medicine, Ayurveda, Yoga and Naturopathy, Unani, Siddha and Sowa-Rigpa, and Homeopathy, use natural self-healing abilities of body and mind. Their ways to treat non-communicable diseases reduce use of modern drugs with their side-effects. Scientific acceptance requires them to be explained from a modern biological perspective. This paper indicates how to achieve such an integrative approach, using aspects of biology not yet taught in medical schools. METHODS: A new, 'Sandwich Model' of biology is introduced that includes holistic epigenetic regulation; also, complexity biology's concept of self-organized criticality; a systems treatment of organism function from Ayurveda; and Ayurveda's six stages of etiology, Shadkriyakala. RESULTS: Molecular biology is upgraded by the sandwich model's layer of epigenetics, leading to a new, scientific definition of health as optimized regulation. Fractal Physiology then expands this to explain self-healing, used in all AYUSH systems. Ayurveda contributes in two ways: its systems approach yields a holistic understanding of organism functioning, while Shadkriyakala improves our understanding of pathophysiology. DISCUSSION: These additions create an integrative biology; modern biology expands to include AYUSH systems' concepts. It provides a scientific basis for India's plan for integrative medical education, with AYUSH systems treated as equal to modern medicine.

Studies on the effects of oral administration of nutrient mixture, quercetin and red onions on the bioavailability of epigallocatechin gallate from green tea extract.

Epigallocatechin gallate (EGCG), a main anticancer component in green tea, has a poor bioavailability in rats and humans due to oxidation, metabolism and its efflux. It was hypothesized that nutrients that address these problems might result in increased bioavailability. Plasma concentrations of EGCG at various time intervals were determined to calculate and compare the pharmacokinetic parameters after oral administration of green tea extract (GTE) or GTE as a nutrient mixture (E) or E + quercetin (Q)/red onions. In rat studies, supplementation of GTE with other nutrients (E) or E + Q raised the plasma C(max) from 55.29 +/- 1.70 to 61.94 +/- 1.70 ng/mL and 94.44 +/- 1.59 ng/mL, respectively. The corresponding t((1/2)) elimination was 2.04 +/- 0.2 h, 3.63 +/- 0.66 h and 2.28 +/- 0.049 h. The AUC(0-24h) were 510.16 +/- 9.88 for GTE, 601.72 +/- 19.10 ng.h/mL for E and 794.08 +/- 15.27 ng x h/mL (p < or = 0.05) for E + Q. In human studies when GTE was fed as GTE or E or E + red onions, the C(max) values were 348.4 +/- 76.6, 384.0 +/- 78.5 ng/mL and 468.4 +/- 131.4. AUC(0-8h) was 1784.1 +/- 56.06 (GTE), 1971.5 +/- 566.5 ng x h/mL (E) and 2490 +/- 878.1 (E + Q), but the change in t((1/2)) elimination was not significant.In conclusion, it is possible to increase the bioavailability of EGCG by supplementing it with nutrients and quercetin.

A combination of green tea extract, specific nutrient mixture and quercetin: An effective intervention treatment for the regression of N-methyl-N-nitrosourea (MNU)-induced mammary tumors in Wistar rats.

Mammary tumors were developed by intraperitoneal injection of N-methyl-N-nitrosourea (MNU) in 21-day-old, sexually immature female Wistar rats. Injection of MNU was repeated 14 weeks after the first one. When palpable tumors were evident in all of the rats, various dietary treatments were initiated for a period of 8 weeks. The treatments were designed to provide 30 mg green tea extract either alone or as a nutrient mixture (E). E was then expanded to include either a nutrient supplement (N), quercetin (Q) or both (N+Q). At the end of the treatment, tumor size/rat measured in the live rats was significantly lower in the groups receiving E, E+Q, E+N and E+N+Q than in the positive control (PC) group which did not receive any dietary treatment. Tumor number/rat, tumor volume/rat and tumor weight/rat were evaluated after sacrificing the rats on the 60th day. The rats receiving E+N+Q showed significantly lower values for the three parameters as compared to the PC group. The PC group showed 24 carcinomas mostly of grade III severity, while the E+N+Q group had only 6 carcinomas, all of which were of grade II severity.

Effect of nutrient mixture and black grapes on the pharmacokinetics of orally administered (-)epigallocatechin-3-gallate from green tea extract: a human study.

(-)Epigallocatechin-3-gallate (EGCG), a green tea component, has been attributed with anticarcinogenic and antioxidant activities. The extent and rate of absorption of EGCG by the small intestine depends on various factors such as molecular size, lipophilicity, solubility, pKa, gastric and intestinal transit time, lumen pH, membrane permeability and first pass metabolism. The bioavailability of EGCG can be increased by decreasing the presystemic elimination by stabilizing EGCG in the lumen, helping its transfer across the intestinal apical membrane and its accumulation and thus its availability by inhibiting phase I and II enzymes and phase III transporters. In a crossover study, five human volunteers were given a single oral dose of GTE (A), nutrient mixture (NM) containing GTE (B) and formulation B along with black grapes 250 g (C). Blood samples were drawn at 0, 2, 4, 6 and 8 h. The pharmacokinetic parameters were analysed by WinNonLin (Vs 5.0.1.) using a non-compartmental approach. Supplementation with nutrient mixture normally prescribed to cancer patients containing ascorbic acid, selenium, N-acetyl cysteine and other nutrients (formulation B) resulted in an increase of the systemic availability of EGCG by 14% and formulation C further increased it by 13%, thus leading to a total increase of 27%.

Cancer phytotherapeutics: role for flavonoids at the cellular level.

Dietary foods and fruits possess an array of flavonoids with unique chemical structure and diverse bioactivities relevant to cancer. Numerous epidemiological studies have validated the inverse relation between the consumption of flavonoids and the risk of cancer. Flavonoids possess cancer blocking and suppressing effects. Flavonoids modulate various CYPs involved in carcinogen activation and scavenging reactive species formed from carcinogens by CYP-mediated reactions. They induce biosynthesis of several CYPs. They are involved in the regulation of enzymes of phase-II responsible for xenobiotic biotransformation and colon microflora. Since cytochromes P450, P-gp and phase-II enzymes are involved in the metabolism of drugs and in the processes of chemical carcinogenesis, interactions of flavonoids with these systems hold great promise for their therapeutic potential. The role of flavonoids also includes the inhibition of activation of pro-carcinogens, inhibition of proliferation of cancer cells, selective death of cancer cells by apoptosis, inhibition of metastasis and angiogenesis, activation of immune response against cancer cells, modulation of the inflammatory cascade and the modulation of drug resistance. This has greatly extended the goal of cancer therapy from eradicating the affected cells to control of the cancer phenotype. Phytotherapy is being used in combination with other therapies as phytonutrients have been shown to work by nutrient synergy.