Alternative Health-Related Articles & Research Information
Articles by D. Graeme Shaw, M.D.
Other Articles of Interest
Phyllanthus Urinaria & Related Species - Selected Published Scientific Abstracts
The Inhibitory Effect of Chinese Herb Phyllanthus on Hepatitis B Virus in Vitro.
Zhonghua Shi Yan He Lin Chuang, pages 282-285, Sep 11, 1997 by Liu Zhuang, Fu XiXian, Zhang NaiLin, First Teaching Hospital, Beijing Medical University, 100034, China. ISSN: 1003-9279
A total of 7 different preparations of the Chinese herb Phyllanthus were studied for their ability to inhibit hepatitis B virus (HBV) DNA replication, i.e. HBsAg and HBeAg expression in an HBV DNA-transfected cell line (2.2.15 cell line).
All drugs were effective against HBV replication in vitro. Capsule 1 and Tuo Cha Zhen Cao were the most potent anti-HBV extracts of those examined. Both extracts decreased HBsAg expression by nearly 100% at the concentration of 500 mg/litre without toxicity to cell growth. Southern blot hybridization showed that capsule 1 inhibited HBV DNA replication in a dose-dependent manner.
It was further observed that under similar dosage, the drug inhibition of HBsAg and HBeAg expression was lower than that of HBV DNA replication; it is suggested that the production of progeny virus particles was not only inhibited at the level of HBV DNA synthesis, but also probably at the level of translation of viral mRNA.
Phyllanthus Urinaria Ameliorates the Severity of Nutritional Steatohepatitis Both In Vitro and In Vivo.
By Bo Shen, Jun Yu, Shiyan Wang, Chu Eagle S. H., Wong V.W.S., Xin Zhou, Ge Lin, Sung Joseph, Chan Henry. Sep. 10, 2007, Hepatology ISSN 0270-9139
Hepatic oxidative stress plays a critical role in metabolic forms of steatohepatitis. Phyllanthus urinaria, an herbal medicine, has been reported to have potential antioxidant properties. We tested the effects of P. urinaria on nutritional steatohepatitis both in vitro and in vivo.
Immortalized normal hepatocytes (AML-12) or primary hepatocytes were exposed to control, the methionine-and-choline-deficient (MCD) culture medium, in the presence or absence of P. urinaria for 24 hours. Hepatocyte triglyceride, release of alanine aminotransferase, lipoperoxides, and reactive oxygen species production were determined.
Age-matched C57BL/6 and db/db mice were fed control or MCD diet for 10 days with or without P. urinaria. Hepatic steatosis, necroinflammation, triglycerides, and lipid peroxide levels were determined. Hepatic expression of inflammatory factors and lipid regulatory mediators were assayed. P. urinaria reduced steatosis and alanine aminotransferase (ALT) levels in culture of hepatocytes in a dose-dependent manner.
Phyllanthus prevented MCD-induced hepatic fat accumulation and steatohepatitis in mice. This effect was associated with repressed levels of hepatic lipid peroxides, reduced expression of cytochrome P450-2E1, pro-inflammatory tumor necrosis factor alpha, interleukin-6, dampened activation of inflammatory c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB), increased expression of lipolytic cytochrome P450 (Cyp4a10), and suppressed transcriptional activity of lipogenic CCAAT/enhancer binding protein β (C/EBPβ).
Hepatic acyl co-enzyme A oxidase that regulated hepatic beta-oxidation of fatty acid and other lipid regulators were not affected by P. urinaria. In conclusion, P. urinaria effectively alleviated the steatohepatitis induced by the MCD, probably through dampening oxidative stress, ameliorating inflammation, and decreasing lipid accumulation.
A Flavonoid from Medicinal Plants Blocks Hepatitis B Virus-e Antigen Secretion in HBV-infected Hepatocytes.
by Shin MS, Kang EH, Lee YI. Antiviral Res. 2005 Sep;67(3):163-8.
Liver Cell Signal Transduction Laboratory, Bioscience Research Division, Korea Research Institute of Bioscience and Biotechnology, Korea.
A flavonoid molecule that showed a unique anti-HBV function was isolated from Phyllanthus urinaria. The molecular formula was determined as C14H6O8 based on FAM-MS analysis and the structure was determined by NMR. The identified flavonoid molecule, ellagic acid, showed unique anti-HBV functions. Ellagic acid did not inhibit either HBV polymerase activity, HBV replication or block HBsAg secretion.
Rather, ellagic acid blocks effectively HBeAg secretion in HepG2 2.2.15 cells (IC50=0.07 microg/ml). Since HBeAg is involved in immune tolerance during HBV infection, ellagic acid, a newly identified functional anti-HBV compound, may be a new candidate therapeutic against immune tolerance in HBV-infected individuals.
Acetone, Ethanol & Methanol Extracts of Phyllanthus Urinaria Inhibit HSV-2 Infection in Vitro.
By Yang CM, Cheng HY, Lin TC, Chiang LC, Lin CC. Taiwan. Antiviral Res. 2005 Jul;67(1):24-30.
Phyllanthus urinaria Linnea (Euphorbiaceae) is one of the traditional medicinal plants that are widely applied by oriental people, especially by Chinese and Indian, to ameliorate various kinds of ailments. Many biological activities, including anti-hepatitis B virus, anti-Epstein-Barr virus and anti-retroviral reverse transcriptase, of P. urinaria have been reported, but not against herpes simplex virus (HSV).
In this study, the anti-HSV-1 and HSV-2 activities of different solvents extracted from P. urinaria were investigated in vitro by plaque reduction assay. Results showed that acetone, ethanol and methanol extracts of P. urinaria inhibited HSV-2 but not HSV-1 infection. The 50% inhibitory concentration against HSV-2 infection (IC50) of acetone, ethanol and methanol extracts was 4.3 +/- 0.5, 5.0 +/ -0.4 and 4.0 +/- 0.9 mcg/ml, respectively.
All three extracts showed no cytotoxic effect against Vero cells at concentrations of 10.0 mcg/ml or below. The time-of-addition study demonstrated that these three extracts were only effective when added during the HSV-2 infection which, therefore, suggested that they disturb the initial stage of HSV-2 infection. Furthermore, they can diminish virus infectivity without significantly affecting incubation time and temperature.
Therefore, the acetone, ethanol and methanol extracts of P. urinaria were concluded to likely inhibit HSV-2 infection through disturbing the early stage of virus infection and through diminishing the virus infectivity.
Mechanism of Protective Action of Phyllanthus Urinaria L. Against Injuries of Liver Cells
(article in Chinese). By Zhou S, Xu C, Zhou N, Huang Y, Huang L, Chen X, Hu Y, Liao Y. Zhongguo Zhong Yao Za Zhi. 1997 Feb;22(2):109-11.
It has been found out that the carbon tetrachloride (CCl4)-induced increase of serum glutamic-pyruvic transaminase (ALT) and elevation of MDA in liver of mice are significantly lowered by Phyllanthus urinaria in vivo, and the coincubation of isolated rat hepatocytes with Phyllanthus urinaria in vitro significantly inhibits CCl4-induced decrease of mobility of membrane of liver cells and increase of intracellular free Ca2+ ([Ca2+]i) concentrations of liver cells.
suggest that the anti-lipid peroxidation effect and protective action of membrane of Phyllanthus urinaria may be related to its protective action against CCl4-induced liver injuries.
Magnesium Bioavailability from Magnesium Citrate & Magnesium Oxide
Journal of the American College of Nutrition, Vol 9, Issue 1 48-55, Copyright © 1990 by American College of Nutrition (CLINICAL TRIAL) by J. S. Lindberg, M. M. Zobitz, J. R. Poindexter and C. Y. at Center for Mineral Metabolism and Clinical Research, University of Texas, Southwestern Medical Center, Dallas 75235
This study compared magnesium oxide and magnesium citrate with respect to in vitro solubility and in vivo gastrointestinal absorbability. The solubility of 25 mmol magnesium citrate and magnesium oxide was examined in vitro in solutions containing varying amounts of hydrochloric acid (0-24.2 mEq) in 300 ml distilled water intended to mimic achlorhydric to peak acid secretory states.
Magnesium oxide was virtually insoluble in water and only 43% soluble in simulated peak acid secretion (24.2 mEq hydrochloric acid/300 ml).
Magnesium citrate had high solubility even in water (55%) and was substantially more soluble than magnesium oxide in all states of acid secretion. Reprecipitation of magnesium citrate and magnesium oxide did not occur when the filtrates from the solubility studies were titrated to pH 6 and 7 to stimulate pancreatic bicarbonate secretion.
Approximately 65% of magnesium citrate was complexed as soluble magnesium citrate, whereas magnesium complexation was not present in the magnesium oxide system. Magnesium absorption from the two magnesium salts was measured in vivo in normal volunteers by assessing the rise in urinary magnesium following oral magnesium load.
The increment in urinary magnesium following magnesium citrate load (25 mmol) was significantly higher than that obtained from magnesium oxide load (during 4 hours post-load, 0.22 vs 0.006 mg/mg creatinine, p less than 0.05; during second 2 hours post-load, 0.035 vs 0.008 mg/mg creatinine, p less than 0.05).
Thus, magnesium citrate was more soluble and bioavailable than magnesium oxide.
The Aqueous Extract from Artemisia Capillaris
Thunb. inhibits lipopolysaccharide-induced inflammatory response through preventing NF-κB activation inhuman hepatoma cell line and rat liver. International Journal of Molecular Medicine, pp. 717-720, 2004, May. Department of Internal Medicine, Research Institute of Oriental Medicine, Dong-Eui University, Busan 614-052, South Korea
Artemisia capillaris Thunb. has been used for the remedy of liver diseases such as hepatitis, jaundice and fatty liver in traditional oriental medicine.
However, despite extensive pharmacological studies, the molecular mechanism of the anti-inflammatory effect of Artemisia capillaris Thunb. has hardly been studied.
In the present study, we investigated the pharmacological action mechanism on LPS-induced liver inflammation in HepG2 human hepatocarcinoma cells and rat liver. Aqueous extract from Artemisia capillaris Thunb. (AEAC) inhibits expression of inflammatory proteins including iNOS, COX-2 and TNF-alpha.
Also, nuclear translocation of NF-kappaB and degradation of I-kappaBalpha are blocked by AEAC pretreatment. These results suggest that the inhibitory effect of AEAC on the expression of inflammatory proteins involves suppression of NF-kappaB activation.
Oral Artemisinin prevents and delays the development of 7,12-dimethylbenz- [a]anthracene (DMBA)-induced breast cancer in the rat
Cancer Letters , Volume 231 , Issue 1 , Pages 43 – 48, 2005, H . Lai , N . Singh
Artemisinin, a compound isolated from the sweet wormwood Artemisia annua L., has previously been shown to have selective toxicity towards cancer cells in vitro.
In the present experiment, we studied the potential of artemisinin to prevent breast cancer development in rats treated with a single oral dose (50mg/kg) of 7,12-dimethylbenz [a]anthracene (DMBA), known to induce multiple breast tumors.
Starting from the day immediately after DMBA treatment, one group of rats was provided with a powdered rat-chow containing 0.02% artemisinin, whereas a control group was provided with plain powdered food. For 40 weeks, both groups of rats were monitored for breast tumors.
Oral artemisinin significantly delayed (P<.002) and in some animals prevented (57% of artemisinin-fed versus 96% of the controls developed tumors, P<.01) breast cancer development in the monitoring period.
In addition, breast tumors in artemisinin-fed rats were significantly fewer (P<.002) and smaller in size (P<.05) when compared with controls.
Since artemisinin is a relatively safe compound that causes no known side effects even at high oral doses, the present data indicate that artemisinin may be a potent cancer-chemoprevention agent.
Magnesium in Cardiovascular & Other Disorders
American Journal of Health-System Pharmacy. 61(15):1569-1576, August 1, 2004. by Gums, John G.
Purpose. The physiological role and metabolism of magnesium, the causes of magnesium deficiency, clinical data on the benefits of magnesium supplementation, and the management of magnesium deficiency are discussed.
Summary. Magnesium is an often overlooked electrolyte that is essential to life. Magnesium plays a role in more than 300 enzymatic reactions and is critically involved in energy metabolism, glucose utilization, protein synthesis, fatty acid synthesis and breakdown, ATPase functions, and virtually all hormonal reactions.
Magnesium is closely involved in maintaining cellular ionic balance through its association with sodium, potassium, and calcium. Deficiency of magnesium is becoming more common in the U.S. population and may be attributed to decreased dietary consumption and the use of diuretics; in the elderly, magnesium deficiency may be a consequence of reduced appetite, decreased mitochondrial respiratory activity, and increased myocardial collagen.
Conditions that may be associated with magnesium deficiency include hypertension, congestive heart failure, arrhythmia, myocardial infarction, diabetes mellitus, and preeclampsia; in many of these, magnesium supplementation has been found beneficial in clinical studies.
Supplementation should be considered for patients with risk factors for deficiency and should be instituted for patients showing symptoms of deficiency. In addition to instituting supplementation when appropriate, the clinician should identify and correct the underlying cause of the deficiency.
Conclusion. Magnesium deficiency may contribute to pathological processes. Clinicians should consider using magnesium supplementation to prevent deficiency in patients at risk and to treat deficiency when it occurs.
Randomised, cross-over, placebo controlled trial of magnesium citrate in the treatment of chronic persistent leg cramps
Med Sci Monit, 2002; 8(5): CR326-330, by Christine Roffe, Sheila Sills, Peter Crome, Peter Jones
Summary: Nocturnal leg cramps are common and distressing. The only treatment of proven effectiveness is quinine, but this has a number of side effects. Magnesium salts have been shown to reduce leg cramp distress in pregnancy.
This study tests whether magnesium citrate is effective in the treatment of leg cramps in non-pregnant individuals by conducting in a randomized, double-blind, cross-over placebo-controlled trial.
Conclusion: The results suggest that magnesium may be effective in treatment of nocturnal leg cramps. Further evaluation is recommended.
Hepatoprotective effect of Dandelion (Taraxacum officinale) against acute liver injury induced by Carbon tetrachloride in Sprague-Dawley rats
The FASEB Journal. 2007; 21:862.8, by Chungmu Park, Yusi Zhou and Youngsun Song at the Center of Smart Foods & Drugs, Obang-dong, 607, Kimhae, Korea, Republic of
The present study is to investigate the protective effect of dandelion hot water extract (DWE) on liver injury induced by carbon tetrachloride (CCl4) in Sprague-Dawley rats.
Dandelion samples were extracted by hot water and lyophilized. The freeze-dried DWE was dissolved in third distilled water and administered to rats by gavage at 500mg/kg, 2g/kg respectively for 7 consecutive days.
The acute liver injury was induced by carbon tetrachloride (500ul/kg. p.o.) on the eighth day and 24 hours later all rats are sacrificed. The DWE supplement significantly decreased the serum alanine and aspartate aminotransferase (ALT and AST) activity.
Comparing with the CCl4 intoxicated group, the contents of glutathione peroxidase, glutathione reductase and superoxide dismutase increased dose, dependent manner, and mRNA and protein expression levels of cytochrome p450 2E1 significantly decreased in the dandelion administered group.
These results indicate that DWE has protective effect on acute liver inflammation induced by CCl4 in rats.
Other Selected Peer-Reviewed Publications of Interest:
"Refractory idiopathic thrombocytopenic purpura: An integrated approach to treatment", by Ba Hoang, MD, PhD, D. Graeme Shaw, MD. (2003) J. Orthomol. Med. 18, 77-82
by Ba Hoang, MD, PhD, D. Graeme Shaw, MD. Stephen A. Levine, PhD., Cuong Hoang, MD and Pham Phuong, PhD.
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"New approach in asthma treatment using excitatory modulator", by Ba Hoang, MD, PhD, D. Graeme Shaw, MD. Stephen A. Levine, PhD., Cuong Hoang, MD and Pham Phuong, PhD. (2007) Phytotherapy Research (Feb 13;)
"Restoration of cellular energetic balance with L-Carnitine inneuro-bioenergetic approach for cancer prevention and treatment", by Ba Hoang, MD, PhD, Pham Phuong, PhD., D. Graeme Shaw, MD. Stephen A. Levine, PhD (2007) Med Hypotheses
"Bronchial epilepsy or broncho-pulmonary hyper-excitability as a model of asthma pathogenesis", by Ba Hoang, MD, PhD, D. Graeme Shaw, MD. Stephen A. Levine, PhD., Cuong Hoang, MD and Pham Phuong, PhD. (2006) Med Hypotheses 67, 1042-1051.
"A. Neurobiological effects of melatonin as related to cancer", by Ba Hoang, MD, PhD, D. Graeme Shaw, MD. Stephen A. Levine, PhD., and Pham Phuong, PhD. (2007) European Journal of Cancer Prevention
"A. Neuro-bioenergetic concepts in cancer prevention and treatment" by Ba Hoang, MD, PhD, D. Graeme Shaw, MD. Stephen A. Levine, PhD., and Pham Phuong, PhD. (2007) Med Hypotheses. 68, 832-843
"Hypothesis of the cause and development of neoplasms", by Ba Hoang, MD, PhD, D. Graeme Shaw, MD. Stephen A. Levine, PhD., and Pham Phuong, PhD. (2007) European Journal of Cancer Prevention, 16, 55-61