Herbal Antioxidants and Protection from Radiation

Introduction to antioxidants

An antioxidant is a molecule capable of slowing or preventing the oxidation of other molecules. Oxidation reactions can produce free radicals, which start chain reactions that damage cells.  Antioxidants stop these chain reactions by removing free radicals and inhibit other oxidation reactions by being oxidized themselves. Although oxidation reactions are crucial for life, they can also be damaging. Specific plants, herbs and spices contain a variety of important antioxidants of which many are famous in Asian cooking where they play an important role in dietary health.

Insufficient levels of antioxidants or excessive oxidative stress may damage or kill human cells. Oxidative stress is an important factor in many human diseases. We now have a greater understanding of why certain plants are beneficial in supporting human health due to the potent antioxidant compounds they contain that help replenish our bodies own natural antioxidant defences.

Because they have one or more unpaired electrons, free radicals are highly unstable. They scavenge your body to grab or donate electrons, thereby damaging cells, proteins, and DNA (genetic material). It is impossible for us to avoid damage by free radicals as these arise from sources both inside and outside our bodies. Oxidants that develop from processes within our bodies form as a result of normal aerobic respiration, metabolism, and inflammation. Exogenous free radicals form from environmental factors such as excessive sunlight, strenuous exercise, X-rays, smoking and alcohol. Ever increasing environmental pollution generates additional free radical damage and toxicity overwhelming our already overburdened detoxification systems.

Antioxidant compound target different cellular reactions and cells of different organs and these are now believed to play a role in preventing the development of such chronic diseases as cancer, heart disease, stroke, alzheimer's, rheumatoid arthritis, diabetes, liver disease and cataracts.

Nuclear radiation and free radical damage

The recent concerns about radioactive isotopes being released into the environment as a result of the Fukushima Nuclear Power Plant reactor leakage has the potential to emit some of the most dangerous forms of free radical damage from ionizing radiation. Radioactive elements undergo decay and emit high-energy particles energetic enough to ionize atoms by knocking off their electrons. This ionizing radiation can damage DNA molecules directly, by breaking the bonds between atoms, or it can ionize water molecules and form free radicals (our cells are mostly water and ionizing radiation breaks H20 down into harmful free radicals H+ and OH-), which are highly reactive and also disrupt the bonds of surrounding molecules, including DNA. This DNA damage is enough to kill cells or cause them to mutate in ways that may eventually lead to cancer. The DNA damaging effects of radiation is measured in units called sieverts, which take into account the type and amount of radiation, and which parts of the body are exposed, allowing us to compare different kinds of exposures in one scale. In a typical year, a person might receive a total dose of two or three millisieverts from things like ambient radioactivity, plane flights and medical procedures. 100 millisieverts a year is the limit above which cancer risk starts to increase, according to the World Nuclear Association. The greatest danger is for people living in an affected area and winds can carry radioactive isotopes many hundreds of kilometers (as evidenced from the Chernobyl disaster in Europe), which can accumulate in the body, water table and food chain further damaging tissue over time and causing disease and cancer.

Effects of ionizing radiation

Free radical organ damage depends on which free radical is involved, how high the concentration, the target of damage and predisposing factors. Children are naturally more risk from radiation because their cells typically divide more rapidly than those of adults.  Common sources of radiation are background radiation from space and naturally occurring radioactive elements underground. The most dangerous to human health are those coming from man made radiation sources. These include; medical imaging tests such as x-rays, radiation therapy for cancer, work exposure for those working with such equipment, nuclear fallout and of growing global concern, ionizing radiation released from nuclear power plant accidents. Ionizing radiation produces the most rapid free radical damage to various organs and may produce immediate or delayed damage as follows;

Brain: Nerve cells and brain blood vessels can die, leading to seizures.
Bone Marrow: Radiation exposure can damage the blood forming cells of the bone marrow leading to anemia (low red blood cell count).
Eyes:
Radiation exposure increases the risk of cataracts.

Thyroid: The thyroid is very sensitive to the effects of Radioactive iodine (I-131) (in fact, I-131′s affinity for the thyroid is used therapeutically to specifically attract radiation to the thyroid in order to treat thyroid cancer and overactive thyroid). When a healthy thyroid is exposed to I-131, it can lead to decreased thyroid function and, over time, thyroid cancer.
Lungs: When you breathe in invisible nuclear fallout particles, it can lead to lung cancer.
Heart: High doses of radiation can damage the cells in the blood vessels that feed the heart, reducing cardiac function.
Digestive tract: Sensitive cells in the intestinal lining can be damaged, leading to loss of appetite, nausea, bloody vomiting, and bloody diarrhea.
Reproductive organs: Rapidly dividing cells (eggs and sperm) in the ovaries and testes can die, leading to sterility.
Skin: Rapidly dividing skin cells can be damaged, leading to skin lesions and burn.
Lymphatic organs: Rapidly dividing lymphatic cells die and damaged bone marrow may have trouble replenishing these immune-boosting cells, increasing the risk of infection.
Other effects and symptoms of excessive free radical damage from radiation exposure includes: tumor growth / cancer, hemorrhages under the skin, bleeding from the nose, gums or mouth,  hair loss, weakness and fatigue, fainting, dehydration and inflammation of tissues (swelling, redness or tenderness). Large radiation doses destroys millions of cells and tissues of the body and as such can lead to impairment of any organ function and / or death from organ failure.

Antioxidant protection from free radical damage

The therapeutic benefit of many medicinal plants is a direct result of their antioxidant properties on specific organs and bodily tissues. As such, herbals provide important protection from free radical damage and ionizing radiation. To assist detoxification from high doses of free radicals or radioactive isotopes then an understanding of plant antioxidants and their individual effects is very helpful in selecting the formulations that provide optimal antioxidant components to restore health.

The first step is always to remove oneself from the source of excessive free radicals or area of ionizing radiation exposure and to avoid consuming contaminated foodstuff or drinking contaminated water. Eat a diet high in uncontaminated fresh fruits and vegetables. Studies in Japan have shown a therapeutic effect from consuming a diet high in brown rice, miso soup, vegetables, onions and garlic and abundant seaweed, while also consuming plenty of antioxidant rich green tea. Any diet high in protective nutrients, enzymes and antioxidants will provide higher cellular protection.

Many antioxidant herbs have been studied for their effects as radioprotective agents (able to protect humans from ionizing radiation). In nature, plants have evolved an array of phytochemicals to protect them from the ionizing radiation from the sun and to survive in harsh environments. Tropical herbs and spices in particular have evolved as a response to the intense ultraviolet radiation around the equatorial regions. These herbs have been at the forefront of research into radioprotection as a result of their unique antioxidant effects. They hold immense promise to save human lives in the wake of the rise in global environmental pollution and the potential exposure to nuclear radiation, such as from the recent reactor accident in Fukushima, Japan.

RAINFOREST HERBS ANTIOXIDANT FORMULATIONS

HEMPEDU BUMI PLUS contains a combination of antioxidant-rich herbal extracts: Andrographis paniculata, Curcuma longa and Phyllanthus niruri / amarus.

Andrographis contains a group of active ingredients known as andrographolides that have been shown to have powerful free-radical scavenging properties together with some of the most well researched anticancer, liver protective and immunostimulant properties known in herbal medicine(40–82). Andrographis is now being widely researched for its anti-cancer and anti tumor effects in cancers of the liver, lymphatics, prostate, lungs, colon, leukemia and breast. As a systemic antioxidant that also markedly improves white blood cell immunity and liver detoxification, Andrographis is uniquely suited to protect human health in the face of ionizing radiation.

Cucuma longa contains the active ingredient known as Curcumin, responsible for the yellow colour in curry and which is one of the most popular antioxidant plant supplements worldwide. Together with its effects on improving antioxidant status in various diseases it has also been studied for its radioprotective effects on decreasing the damaging effects of radiation (83-91).

Phyllanthus niruri / amarus it well researched for its liver protective and antiviral effects and is widely used for viral hepatitis infection. It contains ellagitannins that have potent antioxidant and superoxide radical scavenging ability and enhance glutathione. Recent research is also focusing on the plants anticancer and radioprotective effects (131-147).

Body organs / systems protected: This product is designed to offer optimal antioxidant protection for the whole body, with emphasis on the liver, white blood cells, gastro-intestinal system and cardiovascular system. For more info please visit our LIVER and IMMUNITY pages or to purchase click here. Also available as a herbal tea blend.

SELASIH PLUS contains one of the most well researched herbs for protecting from the harmful effects of ionizing radiation; Ocimum sanctum, also known as Asian Holly Basil. Numerous studies have revealed that it contains potent antioxidant flavonoids, orientin and vicenin that protect the white blood cells, chromosomes and bone marrow from radiation poisoning. Protective antioxidant effects were also seen in animal studies after high-dose 131 iodine exposure with increased survival time, prevention of lipid peroxidation and enhanced glutathione (22-35).

Body organs / systems protected: Whole body, antioxidant protection as well as; thyroid, bone marrow / white blood cells, red blood cells. Coming soon in herbal powder sachets.

PEGAGA PLUS contains Centella asiatica (Gotu Kola) that contains potent triterpenoids; asiaticoside, centellic acid and madecassic acid. Centella has been extremely well researched for the past 50 years for its effects on enhancing cellular healing, micro-circulation and brain function. Recent studies have shown Centella asiatica provides radioprotection to DNA and membranes against radiation exposure, as well as prevents radiation-induced decline in antioxidant enzyme levels and the prevention of radiation induced weight loss and taste aversion (6-12). This formulation also includes Andrographis and Orthosiphon (see references).

Body organs / systems protected: Provides bone marrow antioxidant protection from radiation, as well as for skin, blood vessels, brain and nervous system, lungs, and digestive system. To purchase click here.

MISAI KUCING PLUS contains a combination of potent antioxidant herbs, namely; Orthosiphon stamineus / aristatus, Zingiber officinale, Centella asiatica and Curcuma longa.

Also known as Java Tea, the antioxidant properties of Orthosiphon and its polyphenol fractions have been well research in Malaysia in reducing oxidative stress by inhibiting the formation of lipid peroxidation, as well as their use as a cytoprotective against free radical induced cell death (92-103).

Zingiber officinale (Ginger) contains the active ingredient gingerol, well-known for its anti-nausea and anti-inflammatory effects. Recent research is focusing on its antioxidant mechanisms whereby it shows strong potential as an anti-cancer and radioprotective agent to ameliorate symptoms of radiation exposure, such as taste aversion, learning difficulties and digestive disturbances and vomiting (113-116).

Curcuma and Centella (see references) further protect from radiation induced gastrointestinal and bone marrow cellular deaths and assist to reduce the symptoms of radiation sickness.

Body organs / systems protected: Radiation sickness, digestive disturbances; nausea, vomiting, protect skeletal system and bone marrow. To purchase click here.

TONGKAT ALI PLUS contains Eurycoma longifolia, Tinospora cordifolia, Centella asiatica and Glycerrhiza glabra.

Eurycoma longifolia (Tongkat Ali) has been well researched for its effects on promoting testosterone and sperm count and is used as a fertility agent for men.  Eurycoma contains eurycomanone and this has been shown to have anticancer properties via enhancing p53 tumor suppressing protein and directly causing apoptosis of a range of human cancer cells.

Tinospora cordifolia has been widely studied for its radioprotective effects against radiation. It has been found to increase survival time and protect blood and immune cells from damage. Administered before irradiation significantly ameliorated radiation induced elevation in lipid peroxidation and decline in glutathione concentration in testes. These observations indicate the radioprotective potential of Tinospora cordifolia root extract on testicular constituents against gamma irradiation in mice (13-21).

The radioprotective effect of the root extract of Glycyrrhiza glabra on lipid peroxidation and white blood cell status has been studied and the extract was found to protect microsomal membranes (as evident from reduction in lipid peroxidation) DNA, as well as to protect white blood cells (enhancing the recovery of leukocyte count and the blastogenic response).

Body organs / systems protected: Testes / male reproductive, white blood cells, prevents weakness & fatigue. For more information visit our Mens Health page. To purchase click here.

SENDUDUK PLUS

Melastoma malabathricum (Senduduk) has been shown to have marked anti-inflammatory and pain relieving effects and contains high amounts of antioxidants, specifically flavanoids; quercetin, quercitrin and kaempferol. These flavanoids are also responsible for improving energy and relieving fatigue (104-112).

Labisia pumila (Kacip Fatima) is one of the most well known herbs used in Malaysia for indications related to female health and as a tonic after childbirth. It contains phytoestrogenic compounds that have been confirmed in animal models for polycystic ovary disease and post-menopausal osteoporosis. It has been shown to have anti-stress potential and increased response in swimming endurance. A recent study has shown an antioxidant effect against UVB irradiation when applied externally.

Curcuma longa (Turmeric) contains various active constituents, including essential oils and Curcumin with a wide range of pharmacological activities. Curcuma longa has been used extensively in Malaysian and Indonesian herbal medicine for female health and its antioxidant, hepatoprotective and anti-inflammatory effects are widely responsible for its beneficial effects in female health. Current research is focusing on its anti-cancer compounds and for protection from radiation.

Zingiber officinale (Ginger) is familiar as a culinary herb and as a remedy for nausea and indigestion. Its potent anti-inflammatory, antispasmodic and analgesic properties make it a common in Asian herbal medicine. Its active ingredient, gingerol is a potent antioxidant and has been well studied for its protective effects against radiation and has been shown to improve survival and reduce the digestive symptoms and taste aversion after radiation exposure. Studies on breast and ovarian cancer have shown a protective effect.

Body organs / systems protected: Ovaries, white blood cells, prevents weakness & fatigue.  For more information please visit our Womens Health page. To purchase click here.

REFERENCES

Eurycoma longifolia

1.     Effects of Herbal Preparation on Libido and Semen Quality in Boars. Frydrychová S, Opletal L, Macáková K, Lustyková A, Rozkot M, Lipenský J. Reprod Domest Anim. 2010 Nov 23

2.     Eurycoma longifolia Jack in managing idiopathic male infertility. Tambi MI, Imran MK. Asian J Androl. 2010 May;12(3):376-80.

3.     The effect of eurycoma longifolia Jack on spermatogenesis in estrogen-treated rats. Wahab NA, Mokhtar NM, Halim WN, Das S. Clinics (Sao Paulo). 2010;65(1):93-8.

4.     The effect of Eurycoma longifolia on sperm quality of male rats. Chan KL, Low BS, Teh CH, Das PK. Nat Prod Commun. 2009 Oct;4(10):1331-6.

5.     Eurycomanone induce apoptosis in HepG2 cells via up-regulation of p53. Zakaria Y, Rahmat A, Pihie AH, Abdullah NR, Houghton PJ. Cancer Cell Int. 2009 Jun 10;9:16.

Centella asiatica

6.     Protection of DNA and membranes from gamma-radiation induced damages by Centella asiatica. Joy J, Nair CK. J Pharm Pharmacol. 2009 Jul;61(7):941-7.

7.     Radioprotective Potential of Plants and Herbs against the Effects of Ionizing Radiation. C Jagetia G.

8.     J Clin Biochem Nutr. 2007 Mar;40(2):74-81.

9.     Modification of gamma ray induced changes in the mouse hepatocytes by Centella asiatica extract: in vivo studies. Sharma R, Sharma J. Phytother Res. 2005 Jul;19(7):605-11.

10.   Radioprotection of Swiss albino mouse by Centella asiatica extract. Sharma J, Sharma R. Phytother Res. 2002 Dec;16(8):785-6.

11.   Protection against radiation-induced conditioned taste aversion by Centella asiatica. Shobi V, Goel HC. Physiol Behav. 2001 May;73(1-2):19-23.

12.   The effect of tetrandrine and extracts of Centella asiatica on acute radiation dermatitis in rats. Chen YJ, Dai YS, Chen BF, Chang A, Chen HC, Lin YC, Chang KH, Lai YL, Chung CH, Lai YJ. Biol Pharm Bull. 1999 Jul;22(7):703-6.

Tinospora cordifolia

13.   Radiation-Induced Testicular Injury and Its Amelioration by Tinospora cordifolia (An Indian Medicinal Plant) Extract. Sharma P, Parmar J, Sharma P, Verma P, Goyal PK. Evid Based Complement Alternat Med. 2011:643847.

14.   Alteration in the radiosensitivity of HeLa cells by dichloromethane extract of guduchi (Tinospora cordifolia). Rao SK, Rao PS. Integr Cancer Ther. 2010 Dec;9(4):378-84.

15.   Chemopreventive potential of an Indian medicinal plant (Tinospora cordifolia) on skin carcinogenesis in mice. Chaudhary R, Jahan S, Goyal PK. J Environ Pathol Toxicol Oncol. 2008;27(3):233-43.

16.   Effect of Tinospora cordifolia on gamma ray-induced perturbations in macrophages and splenocytes.

17.   Singh L, Tyagi S, Rizvi MA, Goel HC. J Radiat Res (Tokyo). 2007 Jul;48(4):305-15. Epub 2007 Jun 5.

18.   Radioprotective potential of an herbal extract of Tinospora cordifolia. Goel HC, Prasad J, Singh S, Sagar RK, Agrawala PK, Bala M, Sinha AK, Dogra R. J Radiat Res (Tokyo). 2004 Mar;45(1):61-8.

19.   Alteration of lethal effects of gamma rays in Swiss albino mice by Tinospora cordifolia. Pahadiya S, Sharma J. Phytother Res. 2003 May;17(5):552-4.

20.   Free radical scavenging and metal chelation by Tinospora cordifolia, a possible role in radioprotection. Goel HC, Prem Kumar I, Rana SV.Indian J Exp Biol. 2002 Jun;40(6):727-34.

21.   Antioxidant properties of a Tinospora cordifolia polysaccharide against iron-mediated lipid damage and gamma-ray induced protein damage. Subramanian M, Chintalwar GJ, Chattopadhyay S. Redox Rep. 2002;7(3):137-43.

Ocimum sanctum

22.   Antimelanoma and radioprotective activity of alcoholic aqueous extract of different species of Ocimum in C(57)BL mice. Monga J, Sharma M, Tailor N, Ganesh N. Pharm Biol. 2011 Apr;49(4):428-36.

23.   Effect of Ocimum sanctum, turmeric extract and vitamin E supplementation on the salivary gland and bone marrow of radioiodine exposed mice. Bhartiya US, Joseph LJ, Raut YS, Rao BS. Indian J Exp Biol. 2010 Jun;48(6):566-71.

24.   Protective effect of Ocimum sanctum L after high-dose 131iodine exposure in mice: an in vivo study. Bhartiya US, Raut YS, Joseph LJ. Indian J Exp Biol. 2006 Aug;44(8):647-52.

25.   Antioxidant and radioprotective properties of an Ocimum sanctum polysaccharide. Subramanian M, Chintalwar GJ, Chattopadhyay S. Redox Rep. 2005;10(5):257-64.

26.   Radiation protection of human lymphocyte chromosomes in vitro by orientin and vicenin. Vrinda B, Uma Devi P. Mutat Res. 2001 Nov 15;498(1-2):39-46.

27.   Radioprotective, anticarcinogenic and antioxidant properties of the Indian holy basil, Ocimum sanctum (Tulasi). Uma Devi P. Indian J Exp Biol. 2001 Mar;39(3):185-90.

28.   Radiation protection by the ocimum flavonoids orientin and vicenin: mechanisms of action. Uma Devi P, Ganasoundari A, Vrinda B, Srinivasan KK, Unnikrishnan MK. Radiat Res. 2000 Oct;154(4):455-60.

29.   Modulation of glutathione and antioxidant enzymes by Ocimum sanctum and its role in protection against radiation injury. Devi PU, Ganasoundari A. Indian J Exp Biol. 1999 Mar;37(3):262-8.

30.   In vivo radioprotection by ocimum flavonoids: survival of mice. Uma Devi P, Ganasoundari A, Rao BS, Srinivasan KK. Radiat Res. 1999 Jan;151(1):74-8.

31.   A comparative study of radioprotection by Ocimum flavonoids and synthetic aminothiol protectors in the mouse. Devi PU, Bisht KS, Vinitha M. Br J Radiol. 1998 Jul;71(847):782-4.

32.   Enhancement of bone marrow radioprotection and reduction of WR-2721 toxicity by Ocimum sanctum. Ganasoundari A, Devi PU, Rao BS. Mutat Res. 1998 Feb 2;397(2):303-12.

33.   Modification of bone marrow radiosensensitivity by medicinal plant extracts. Ganasoundari A, Zare SM, Devi PU. Br J Radiol. 1997 Jun;70(834):599-602.

34.   Protection against radiation-induced chromosome damage in mouse bone marrow by Ocimum sanctum. Ganasoundari A, Devi PU, Rao MN. Mutat Res. 1997 Feb 3;373(2):271-6.

35.   Radioprotective effect of leaf extract of Indian medicinal plant Ocimum sanctum. Devi PU, Ganasoundari A. Indian J Exp Biol. 1995 Mar;33(3):205-8.

Glycyrrhiza glabra

36.   Evaluation of antioxidant and anti-atherogenic properties of Glycyrrhiza glabra root using in vitro models. Visavadiya NP, Soni B, Dalwadi N. Int J Food Sci Nutr. 2009;60 Suppl 2:135-49. Epub 2009 Apr 22.

37.   Hypocholesterolaemic and antioxidant effects of Glycyrrhiza glabra (Linn) in rats. Visavadiya NP, Narasimhacharya AV. Mol Nutr Food Res. 2006 Nov;50(11):1080-6.

38.   Glycyrrhizae Radix attenuates peroxynitrite-induced renal oxidative damage through inhibition of protein nitration. Yokozawa T, Cho EJ, Rhyu DY, Shibahara N, Aoyagi K. Free Radic Res. 2005 Feb;39(2):203-11.

39.   Protection of DNA and microsomal membranes in vitro by Glycyrrhiza glabra L. against gamma irradiation. Shetty TK, Satav JG, Nair CK. Phytother Res. 2002 Sep;16(6):576-8.

Andrographis paniculata:

40.   Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone andrographolide, the active component of Andrographis paniculata. Yang S, Evens AM, Prachand S, Singh AT, Bhalla S, David K, Gordon LI. Clin Cancer Res. 2010 Oct 1;16(19):4755-68. Epub 2010 Aug 26.

41.   14-Deoxyandrographolide desensitizes hepatocytes to tumour necrosis factor-alpha-induced apoptosis through calcium-dependent tumour necrosis factor receptor superfamily member 1A release via the NO/cGMP pathway. Roy DN, Mandal S, Sen G, Mukhopadhyay S, Biswas T. Br J Pharmacol. 2010 Aug;160(7):1823-43.

42.   [Effects of angrographolide on plasma glucose level of experiment diabetic rats and its molecular mechanism]. Yang P, Chen SZ, Xiao SJ, Hou QY, Zhou YQ, Feng M, Li L. Zhong Yao Cai. 2009 Oct;32(10):1577-9. Chinese.

43.   Absorption of andrographolides from Andrographis paniculata and its effect on CCl(4)-induced oxidative stress in rats. Akowuah GA, Zhari I, Mariam A, Yam MF. Food Chem Toxicol. 2009 Sep;47(9):2321-6. Epub 2009 Jun 18.

44.   Oxidative stress in the brain of nicotine-induced toxicity: protective role of Andrographis paniculata Nees and vitamin E. Das S, Gautam N, Dey SK, Maiti T, Roy S. Appl Physiol Nutr Metab. 2009 Apr;34(2):124-35.

45.   Evaluation of beneficial effects of antioxidant properties of aqueous leaf extract of Andrographis paniculata in STZ-induced diabetes. Dandu AM, Inamdar NM. Pak J Pharm Sci. 2009 Jan;22(1):49-52.

46.   Antioxidant, antioedema and analgesic activities of Andrographis paniculata extracts and their active constituent andrographolide. Lin FL, Wu SJ, Lee SC, Ng LT. Phytother Res. 2009 Jul;23(7):958-64.

47.   In vitro nicotine induced superoxide mediated DNA fragmentation in lymphocytes: protective role of Andrographis paniculata Nees. Das S, Neogy S, Gautam N, Roy S. Toxicol In Vitro. 2009 Feb;23(1):90-8. Epub 2008 Nov 5.

48.   Analysis of urinary andrographolides and antioxidant status after oral administration of Andrographis paniculata leaf extract in rats. Akowuah GA, Zhari I, Mariam A. Food Chem Toxicol. 2008 Dec;46(12):3616-20. Epub 2008 Sep 11.

49.   Andrographolide sensitizes cancer cells to TRAIL-induced apoptosis via p53-mediated death receptor 4 up-regulation. Zhou J, Lu GD, Ong CS, Ong CN, Shen HM. Mol Cancer Ther. 2008 Jul;7(7):2170-80.

50.   Free radical induced damages to rat liver subcellular organelles: inhibition by Andrographis paniculata extract. Tripathi R, Kamat JP. Indian J Exp Biol. 2007 Nov;45(11):959-67.

51.   Antioxidant action of Andrographis paniculata on lymphoma. Verma N, Vinayak M. Mol Biol Rep. 2008 Dec;35(4):535-40.

52.   Hepatoprotective effect of andrographolide against hexachlorocyclohexane-induced oxidative injury. Trivedi NP, Rawal UM, Patel BP. Integr Cancer Ther. 2007 Sep;6(3):271-80.

53.   Hepatoprotective effect of leaf extracts of Andrographis lineata nees on liver damage caused by carbon tetrachloride in rats. Sangameswaran B, Reddy TC, Jayakar B. Phytother Res. 2008 Jan;22(1):124-6.

54.   Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice. Singha PK, Roy S, Dey S. J Ethnopharmacol. 2007 Apr 20;111(1):13-21.

55.   Antioxidant and anti-inflammatory activities of the plant Andrographis paniculata Nees. Sheeja K, Shihab PK, Kuttan G. Immunopharmacol Immunotoxicol. 2006;28(1):129-40.

56.   Mechanism of the superoxide scavenging activity of neoandrographolide - a natural product from Andrographis paniculata Nees. Kamdem RE, Sang S, Ho CT. J Agric Food Chem. 2002 Jul 31;50(16):4662-5.

57.   Modulatory influence of Andrographis paniculata on mouse hepatic and extrahepatic carcinogen metabolizing enzymes and antioxidant status. Singh RP, Banerjee S, Rao AR. Phytother Res. 2001 Aug;15(5):382-90.

58.   Hepatoprotective and antioxidant property of Andrographis paniculata (Nees) in BHC induced liver damage in mice. Trivedi NP, Rawal UM. Indian J Exp Biol. 2001 Jan;39(1):41-6.

59.   Antihyperglycaemic and anti-oxidant properties of Andrographis paniculata in normal and diabetic rats. Zhang XF, Tan BK. Clin Exp Pharmacol Physiol. 2000 May-Jun;27(5-6):358-63.

60.   Andrographolide, an herbal medicine, inhibits interleukin-6 expression and suppresses prostate cancer cell growth. Chun JY, Tummala R, Nadiminty N, Lou W, Liu C, Yang J, Evans CP, Zhou Q, Gao AC. Genes Cancer. 2010 Aug 1;1(8):868-876.

61.   Andrographolide down-regulates hypoxia-inducible factor-1α in human non-small cell lung cancer A549 cells. Lin HH, Tsai CW, Chou FP, Wang CJ, Hsuan SW, Wang CK, Chen JH. Toxicol Appl Pharmacol. 2011 Feb 1;250(3):336-45. Epub 2010 Dec 4.

62.   Andrographis paniculata downregulates proinflammatory cytokine production and augments cell mediated immune response in metastatic tumor-bearing mice. Sheeja K, Kuttan G. Asian Pac J Cancer Prev. 2010;11(3):723-9.

63.   Andrographolide exhibits anti-invasive activity against colon cancer cells via inhibition of MMP2 activity. Chao HP, Kuo CD, Chiu JH, Fu SL. Planta Med. 2010 Nov;76(16):1827-33. Epub 2010 Jun 10.

64.   Inhibitory effects of andrographolide on migration and invasion in human non-small cell lung cancer A549 cells via down-regulation of PI3K/Akt signaling pathway. Lee YC, Lin HH, Hsu CH, Wang CJ, Chiang TA, Chen JH. Eur J Pharmacol. 2010 Apr 25;632(1-3):23-32. Epub 2010 Jan 25.

65.   Potency of andrographolide as an antitumor compound in BHC-induced liver damage. Trivedi NP, Rawal UM, Patel BP. Integr Cancer Ther. 2009 Jun;8(2):177-89.

66.   Andrographolide inhibits growth of acute promyelocytic leukaemia cells by inducing retinoic acid receptor-independent cell differentiation and apoptosis. Manikam, Shiamala T, J Pharm Pharmacol. 2009 May;61(5):687.

67.   Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G(1) arrest and apoptosis. Jada SR, Matthews C, Saad MS, Hamzah AS, Lajis NH, Stevens MF, Stanslas J. Br J Pharmacol. 2008 Nov;155(5):641-54. Epub 2008 Sep 22.

68.   Anti-tumor activities of andrographolide, a diterpene from Andrographis paniculata, by inducing apoptosis and inhibiting VEGF level. Zhao F, He EQ, Wang L, Liu K. J Asian Nat Prod Res. 2008 May-Jun;10(5-6):467-73.

69.   Antioxidant action of Andrographis paniculata on lymphoma. Verma N, Vinayak M. Mol Biol Rep. 2008 Dec;35(4):535-40.

70.   Hepatoprotective effect of andrographolide against hexachlorocyclohexane-induced oxidative injury. Trivedi NP, Rawal UM, Patel BP. Integr Cancer Ther. 2007 Sep;6(3):271-80.

71.   Activation of cytotoxic T lymphocyte responses and attenuation of tumor growth in vivo by Andrographis paniculata extract and andrographolide. Sheeja K, Kuttan G. Immunopharmacol Immunotoxicol. 2007;29(1):81-93.

72.   Modulation of natural killer cell activity, antibody-dependent cellular cytotoxicity, and antibody-dependent complement-mediated cytotoxicity by andrographolide in normal and Ehrlich ascites carcinoma-bearing mice. Sheeja K, Kuttan G. Integr Cancer Ther. 2007 Mar;6(1):66-73.

73.   Ameliorating effects of Andrographis paniculata extract against cyclophosphamide-induced toxicity in mice. Sheeja K, Kuttan G. Asian Pac J Cancer Prev. 2006 Oct-Dec;7(4):609-14.

74.   Semisynthesis and in vitro anticancer activities of andrographolide analogues. Jada SR, Subur GS, Matthews C, Hamzah AS, Lajis NH, Saad MS, Stevens MF, Stanslas J. Phytochemistry. 2007 Mar;68(6):904-12. Epub 2007 Jan 17.

75.   Apoptosis inducing effect of andrographolide on TD-47 human breast cancer cell line. Sukardiman H, Widyawaruyanti A, Sismindari, Zaini NC. Afr J Tradit Complement Altern Med. 2007 Feb 16;4(3):345-51.

76.   Protective effect of Andrographis paniculata and andrographolide on cyclophosphamide-induced urothelial toxicity. Sheeja K, Kuttan G. Integr Cancer Ther. 2006 Sep;5(3):244-51.

77.   Andrographolide isolated from Andrographis paniculata induces cell cycle arrest and mitochondrial-mediated apoptosis in human leukemic HL-60 cells. Cheung HY, Cheung SH, Li J, Cheung CS, Lai WP, Fong WF, Leung FM. Planta Med. 2005 Dec;71(12):1106-11.

78.   Morphological and biochemical changes of andrographolide-induced cell death in human prostatic adenocarcinoma PC-3 cells. Kim TG, Hwi KK, Hung CS. In Vivo. 2005 May-Jun;19(3):551-7.

79.   Anticancer and immunostimulatory compounds from Andrographis paniculata. Kumar RA, Sridevi K, Kumar NV, Nanduri S, Rajagopal S. J Ethnopharmacol. 2004 Jun;92(2-3):291-5.

80.   Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata. Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R. J Exp Ther Oncol. 2003 May-Jun;3(3):147-58.

81.   Modulatory influence of Andrographis paniculata on mouse hepatic and extrahepatic carcinogen metabolizing enzymes and antioxidant status. Singh RP, Banerjee S, Rao AR. Phytother Res. 2001 Aug;15(5):382-90.

82.   Hepatoprotective and antioxidant property of Andrographis paniculata (Nees) in BHC induced liver damage in mice. Trivedi NP, Rawal UM. Indian J Exp Biol. 2001 Jan;39(1):41-6.

Curcuma longa

83.   Suppression of mitochondrial NADP(+)-dependent isocitrate dehydrogenase activity enhances curcumin-induced apoptosis in HCT116 cells. Jung KH, Park JW. Free Radic Res. 2011 Apr;45(4):431-8. Epub 2010 Nov 29.

84.   Free radical scavenging activity and characterization of sesquiterpenoids in four species of Curcuma using a TLC bioautography assay and GC-MS analysis. Zhao J, Zhang JS, Yang B, Lv GP, Li SP.Molecules. 2010 Oct 27;15(11):7547-57.

85.   Curcumin supplementation could improve diabetes-induced endothelial dysfunction associated with decreased vascular superoxide production and PKC inhibition. Rungseesantivanon S, Thenchaisri N, Ruangvejvorachai P, Patumraj S. BMC Complement Altern Med. 2010 Oct 14;10:57.

86.   Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Goel A, Aggarwal BB. Nutr Cancer. 2010;62(7):919-30. Review.

87.   Curcumin attenuates the effects of transport stress on serum cortisol concentration, hippocampal NO production, and BDNF expression in the pig. Wei S, Xu H, Xia D, Zhao R. Domest Anim Endocrinol. 2010 Nov;39(4):231-9. Epub 2010 Jul 30.

88.   The protective effects of Curcuma longa Linn. extract on carbon tetrachloride-induced hepatotoxicity in rats via upregulation of Nrf2. Lee HS, Li L, Kim HK, Bilehal D, Li W, Lee DS, Kim YH. J Microbiol Biotechnol. 2010 Sep;20(9):1331-8.

89.   Effect of Ocimum sanctum, turmeric extract and vitamin E supplementation on the salivary gland and bone marrow of radioiodine exposed mice. Bhartiya US, Joseph LJ, Raut YS, Rao BS. Indian J Exp Biol. 2010 Jun;48(6):566-71.

90.   Anti-breast cancer activity of curcumin on the human oxidation-resistant cells ZR-75-1 with gamma-glutamyltranspeptidase inhibition. Quiroga A, Quiroga PL, Martínez E, Soria EA, Valentich MA. J Exp Ther Oncol. 2010;8(3):261-6.

91.   Separation of curcuminoids enriched fraction from spent turmeric oleoresin and its antioxidant potential. Nagarajan S, Kubra IR, Rao LJ. J Food Sci. 2010 Aug 1;75(6):H158-62.

Orthosiphon sp.

92.   Antiapoptotic and Antioxidant Properties of Orthosiphon stamineus Benth (Cat's Whiskers): Intervention in the Bcl-2-Mediated Apoptotic Pathway, Siddig Ibrahim Abdelwahab et al. Evid Based Complement Alternat Med. 2011; 2011: 156765.

93.   Radical scavenging activity of methanol leaf extracts of Orthosiphon stamineus. Akowuah GA, Zhari I, Norhayati I, Sadikun A. Pharmaceutical Biology. 2004;42(8):629–635.

94.   Sinensetin, eupatorin, 3-hydroxy-5, 6, 7, 4 -tetramethoxyflavone and rosmarinic acid contents and antioxidative effect of Orthosiphon stamineus from Malaysia. Akowuah GA, Zhari I, Norhayati I, Sadikun A, Khamsah SM. Food Chemistry. 2004;87(4):559–566.

95.   HPTLC densitometric analysis of Orthosiphon stamineus leaf extracts and inhibitory effect on xanthine oxidase activity. Akowuah GA, Zhari I, Sadikun A, Norhayati I. Pharmaceutical Biology. 2006;44(1):65–70.

96.   Quantification of Betulinic acid in leaf extracts of Orthosiphon stamineus. \Akowuah GA, Zhari I, Sadikun A, Norhayati I, Sundram K, Khamsah M. Journal of Tropical Medicinal Plants. 2003;4(2):225–228.

97.   Screening of several Indonesian medicinal plants for their inhibitory effect on histamine release from RBL-2H3 cells. Ikawati Z, Wahyuono S, Maeyama K. Journal of Ethnopharmacology. 2001;75(2-3):249–256.

98.   Inhibition of NO production by highly-oxygenated diterpenes of Orthosiphon stamineus and their structure-activity relationship. Awale S, Tezuka Y, Banskota AH, Kadota S. Biological and Pharmaceutical Bulletin. 2003;26(4):468–473.

99.   Adenosine A receptor binding activity of methoxy flavonoids from Orthosiphon stamineus. Yuliana ND, Khatib A, Link-Struensee AMR, et al. Planta Medica. 2009;75(2):132–136.

100.Selective extraction of caffeic acid derivatives from Orthosiphon stamineus Benth. (Lamiaceae) leaves. Olah NK, Hanganu D, Oprean R, Mogoşan C, Dubei N, Gocan S. Journal of Planar Chromatography—Modern TLC. 2004;17(1):18–21.

101.High-performance liquid chromatography with diode-array ultraviolet detection of methoxylate flavones in Orthosiphon leaves. Pietta PG, Mauri PL, Gardana C, Bruno A. Journal of Chromatography. 1991;547(1-2):439–442.

102.Four highly oxygenated isopimarane-type diterpenes of Orthosiphon stamineus. Awale S, Tezuka Y, Banskota AH, Kouda K, Kyaw MT, Kadota S. Planta Medica. 2002;68(3):286–288.

103.Flavonoids and triterpenoids from the leaves of Orthosiphon stamineus. Hossain NP, Ismail Z. Journal-Bangladesh Academy of Sciences. 2005;29(1):p. 41.

Melastoma malabathricum

104.Effects of abiotic stress on biomass and anthocyanin production in cell cultures of Melastoma malabathricum. Chan LK, Koay SS, Boey PL, Bhatt A. Molecules. 2010 Nov 29;15(12):8602-17.

105.Antioxidant capacities and total phenolic contents of 56 wild fruits from South China. Fu L, Xu BT, Xu XR, Qin XS, Gan RY, Li HB. Molecules. 2010 Nov 29;15(12):8602-17.

106.Amides, triterpene and flavonoids from the leaves of Melastoma malabathricum L. Sirat HM, Susanti D, Ahmad F, Takayama H, Kitajima M. J Nat Med. 2010 Oct;64(4):492-5.

107.Antidiarrhoeal Activity of Leaves of Melastoma malabathricum Linn. Sunilson JA, Anandarajagopal K, Kumari AV, Mohan S. Indian J Pharm Sci. 2009 Nov;71(6):691-5.

108.Antioxidant activity and polyphenol content in edible wild fruits from Nepal. Chalise JP, Acharya K, Gurung N, Bhusal RP, Gurung R, Skalko-Basnet N, Basnet P. Int J Food Sci Nutr. 2010 Jun;61(4):425-32.

109.[Comparison of flavonoids in medicinal plants Melastoma]. Tang TX, Wu H, Li QG. Zhong Yao Cai. 2007 Aug;30(8):912-3. Chinese.

110.Antinociceptive, anti-inflammatory and antipyretic properties of Melastoma malabathricum leaves aqueous extract in experimental animals. Zakaria ZA, Raden Mohd Nor RN, Hanan Kumar G, Abdul Ghani ZD, Sulaiman MR, Rathna Devi G, Mat Jais AM, Somchit MN, Fatimah CA. Can J Physiol Pharmacol. 2006 Dec;84(12):1291-9.

111.Antinociceptive effect of Melastoma malabathricum ethanolic extract in mice. Sulaiman MR, Somchit MN, Israf DA, Ahmad Z, Moin S. Fitoterapia. 2004 Dec;75(7-8):667-72.

112.Monoamine oxidase B and free radical scavenging activities of natural flavonoids in Melastoma candidum D. Don. Lee MH, Lin RD, Shen LY, Yang LL, Yen KY, Hou WC. J Agric Food Chem. 2001 Nov;49(11):5551-5.

Zingiber officinale

113.[6]-Gingerol attenuates β-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system. Lee C, Park GH, Kim CY, Jang JH. Food Chem Toxicol. 2011 Mar 15. [Epub ahead of print]

114.Zingiber officinale protects HaCaT cells and C57BL/6 mice from ultraviolet B-induced inflammation. Guahk GH, Ha SK, Jung HS, Kang C, Kim CH, Kim YB, Kim SY. J Med Food. 2010 Jun;13(3):673-80.

115.Antioxidant and inhibitory effect of red ginger (Zingiber officinale var. Rubra) and white ginger (Zingiber officinale Roscoe) on Fe(2+) induced lipid peroxidation in rat brain in vitro. Oboh G, Akinyemi AJ, Ademiluyi AO. Exp Toxicol Pathol. 2010 Jul 1.

116.Appl Physiol Nutr Metab. 2010 Apr;35(2):134-41.

117.Protective effects of dietary ginger (Zingiber officinales Rosc.) on lindane-induced oxidative stress in rats. Ahmed RS, Suke SG, Seth V, Chakraborti A, Tripathi AK, Banerjee BD. Phytother Res. 2008 Jul;22(7):902-6.

118.Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells. Rhode J, Fogoros S, Zick S, Wahl H, Griffith KA, Huang J, Liu JR. BMC Complement Altern Med. 2007 Dec 20;7:44.

119.Cancer preventive properties of ginger: a brief review. Shukla Y, Singh M. Food Chem Toxicol. 2007 May;45(5):683-90

120.[6]-Gingerol prevents UVB-induced ROS production and COX-2 expression in vitro and in vivo. Kim JK, Kim Y, Na KM, Surh YJ, Kim TY. Free Radic Res. 2007 May;41(5):603-14.

121.Zingiber officinale exhibits behavioral radioprotection against radiation-induced CTA in a gender-specific manner. Haksar A, Sharma A et al. Pharmacol Biochem Behav. 2006 Jun;84(2):179-88.

122.Int J Dermatol. 2006 Apr;45(4):460-8.

123.Anal Bioanal Chem. 2006 Aug;385(7):1241-6.

124.Zingiber officinale Rosc. modulates gamma radiation-induced conditioned taste aversion. Sharma A, Haksar A, Chawla R, Kumar R, Arora R, Singh S, Prasad J, Islam F, Arora MP, Kumar Sharma R. Pharmacol Biochem Behav. 2005 Aug;81(4):864-70.

125.Ginger (Zingiber officinale Rosc.), a dietary supplement, protects mice against radiation-induced lethality: mechanism of action. Jagetia G, Baliga M, Venkatesh P. Cancer Biother Radiopharm. 2004 Aug;19(4):422-35.

126.Influence of ginger rhizome (Zingiber officinale Rosc) on survival, glutathione and lipid peroxidation in mice after whole-body exposure to gamma radiation. Jagetia GC, Baliga MS, Venkatesh P, Ulloor JN. Radiat Res. 2003 Nov;160(5):584-92.

Labisia pumila

127.Protective effect of Labisia pumila on stress-induced behavioral, biochemical, and immunological alterations. Kour K, Sharma N, Chandan BK, Koul S, Sangwan PL, Bani S. Planta Med. 2010 Oct;76(14):1497-505.

128.Labisia pumila extract protects skin cells from photoaging caused by UVB irradiation. Choi HK, Kim DH, Kim JW, Ngadiran S, Sarmidi MR, Park CS. J Biosci Bioeng. 2010 Mar;109(3):291-6

129.Beneficial metabolic effects of the Malaysian herb Labisia pumila var. alata in a rat model of polycystic ovary syndrome. Mannerĺs L, Fazliana M, Wan Nazaimoon WM, Lönn M, Gu HF, Ostenson CG, Stener-Victorin E. J Ethnopharmacol. 2010 Feb 3;127(2):346-51.

130.Labisia pumila extract regulates body weight and adipokines in ovariectomized rats. Fazliana M, Wan Nazaimoon WM, Gu HF, Ostenson CG. Maturitas. 2009 Jan 20;62(1):91-7.

Phyllanthis amarus / niruri

131.Radioprotective properties of polyphenols from Phyllanthus amarus Linn. Londhe JS, Devasagayam TP, Foo LY, Ghaskadbi SS. J Radiat Res (Tokyo). 2009 Jul;50(4):303-9.

132.Anti-tumor activity of Phyllanthus niruri (a medicinal plant) on chemical-induced skin carcinogenesis in mice. Sharma P, Parmar J, Verma P, Sharma P, Goyal PK. Asian Pac J Cancer Prev. 2009;10(6):1089-94.

133.An extract of Phyllanthus amarus protects mouse chromosomes and intestine from radiation induced damages. Harikumar KB, Kuttan R. J Radiat Res (Tokyo). 2007 Nov;48(6):469-76.

134.Protective effect of an extract of Phyllanthus amarus against radiation-induced damage in mice. Kumar KB, Kuttan R. J Radiat Res (Tokyo). 2004 Mar;45(1):133-9.

135.The effects of Phyllanthus niruri aqueous extract on the activation of murine lymphocytes and bone marrow-derived macrophages. Nworu CS, Akah PA, Okoye FB, Proksch P, Esimone CO. Immunol Invest. 2010 Jan;39(3):245-67.

136.Antioxidant potential of aqueous extract of Phyllanthus amarus in rats. Karuna R, Reddy SS, Baskar R, Saralakumari D. Indian J Pharmacol. 2009 Apr;41(2):64-7.

137.Aqueous extract of Phyllanthus amarus inhibits chromium(VI)-induced toxicity in MDA-MB-435S cells. Guha G, Rajkumar V, Ashok Kumar R, Mathew L. Food Chem Toxicol. 2010 Jan;48(1):396-401.

138.Phyllanthus urinaria increases apoptosis and reduces telomerase activity in human nasopharyngeal carcinoma cells. Huang ST, Wang CY, Yang RC, Chu CJ, Wu HT, Pang JH. Forsch Komplementmed. 2009 Feb;16(1):34-40.

139.Antioxidant activity of some polyphenol constituents of the medicinal plant Phyllanthus amarus Linn. Londhe JS, Devasagayam TP, Foo LY, Ghaskadbi SS. Redox Rep. 2008;13(5):199-207.

140.NaCl as a physiological modulator of proline metabolism and antioxidant potential in Phyllanthus amarus. Jaleel CA, Manivannan P, Lakshmanan GM, Sridharan R, Panneerselvam R. C R Biol. 2007 Nov;330(11):806-13.

141.An extract of Phyllanthus amarus protects mouse chromosomes and intestine from radiation induced damages. Harikumar KB, Kuttan R. J Radiat Res (Tokyo). 2007 Nov;48(6):469-76.

142.Hepatocytes are protected by herb Phyllanthus niruri protein isolate against thioacetamide toxicity. Sarkar MK, Sil PC. Pathophysiology. 2007 Oct;14(2):113-20.

143.Phenolic antioxidants from the whole plant of Phyllanthus urinaria. Xu M, Zha ZJ, Qin XL, Zhang XL, Yang CR, Zhang YJ. Chem Biodivers. 2007 Sep;4(9):2246-52.

144.Hepatoprotective activity of Phyllanthus amarus Schum. et. Thonn. extract in ethanol treated rats: in vitro and in vivo studies. Pramyothin P, Ngamtin C, Poungshompoo S, Chaichantipyuth C. J Ethnopharmacol. 2007 Nov 1;114(2):169-73.

145.Protein isolate from the herb, Phyllanthus niruri L. (Euphorbiaceae), plays hepatoprotective role against carbon tetrachloride induced liver damage via its antioxidant properties. Bhattacharjee R, Sil PC. Food Chem Toxicol. 2007 May;45(5):817-26.

146.Hepatoprotective effect of aqueous extract of Phyllanthus niruri on nimesulide-induced oxidative stress in vivo. Chatterjee M, Sil PC. Indian J Biochem Biophys. 2006 Oct;43(5):299-305.

147.Protective effect of an extract of Phyllanthus amarus against radiation-induced damage in mice. Kumar KB, Kuttan R. J Radiat Res (Tokyo). 2004 Mar;45(1):133-9