Evidence-Based Efficacy of Adaptogens in Fatigue, and Molecular Mechanisms Related to Their Stress-Protective Activity.

Curr Clin Pharmacol. 2009 Sep 1; Panossian A, Wikman GThe aim of this review article is to assess the level of scientific evidence presented by clinical trials of adaptogens in fatigue, and to provide a rationale at the molecular level for verified effects. Strong scientific evidence is available for Rhodiola rosea SHR-5 extract, which improved attention, cognitive function and mental performance in fatigue and in chronic fatigue syndrome. Good scientific evidence has been documented in trails in which Schisandra chinensis and Eleutherococcus senticosus increased endurance and mental performance in patients with mild fatigue and weakness. Based on their efficacy in clinical studies, adaptogens can be defined as a pharmacological group of herbal preparations that increase tolerance to mental exhaustion and enhance attention and mental endurance in situations of decreased performance. The beneficial stress-protective effect of adaptogens is related to regulation of homeostasis via several mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the control of key mediators of stress response such as molecular chaperons (e.g. Hsp70), stress-activated c-Jun N-terminal protein kinase (JNK1), Forkhead Box O transcription factor DAF-16, cortisol and nitric oxide (NO). The key point of action of phytoadaptogens appears to be their up-regulating and stress-mimetic effects on the "stress-sensor" protein Hsp70, which plays an important role in cell survival and apoptosis. Hsp70 inhibits the expression of NO synthase II gene and interacts with glucocorticoid receptors directly and via the JNK pathway, thus affecting the levels of circulating cortisol and NO. Prevention of stress-induced increase in NO, and the associated decrease in ATP production, results in increased performance and endurance. Adaptogen-induced up-regulation of Hsp70 triggers stress-induced JNK-1 and DAF-16-mediated pathways regulating the resistance to stress and resulting in enhanced mental and physical performance and, possibly, increased longevity.

Anti-parasitic activity and cytotoxicity of selected medicinal plants from Kenya.

J Ethnopharmacol. 2009 Jun 25; 123(3): 504-9Kigondu EV, Rukunga GM, Keriko JM, Tonui WK, Gathirwa JW, Kirira PG, Irungu B, Ingonga JM, Ndiege IOIndigenous rural communities in the tropics manage parasitic diseases, like malaria and leishmaniasis, using herbal drugs. The efficacy, dosage, safety and active principles of most of the herbal preparations are not known. Extracts from 6 selected plant species, used as medicinal plants by indigenous local communities in Kenya, were screened for in vitro anti-plasmodial and anti-leishmanial activity, against 2 laboratory-adapted Plasmodium falciparum isolates (D6, CQ-sensitive and W2, CQ-resistant) and Leishmania major (IDU/KE/83=NLB-144 strain), respectively. The methanol extract of Suregada zanzibariensis leaves exhibited good anti-plasmodial activity (IC(50) 4.66+/-0.22 and 1.82+/-0.07 microg/ml for D6 and W2, respectively). Similarly, the methanol extracts of Albizia coriaria (IC(50) 37.83+/-2.11 microg/ml for D6) and Aspergillus racemosus (32.63+/-2.68 and 33.95+/-2.05 microg/ml for D6 and W2, respectively) had moderate anti-plasmodial activity. Acacia tortilis (IC(50) 85.73+/-3.36 microg/ml for W2) and Albizia coriaria (IC(50) 71.17+/-3.58 microg/ml for W2) methanol extracts and Aloe nyeriensis var kedongensis (IC(50) 87.70+/-2.98 and 67.84+/-2.12 microg/ml for D6 and W2, respectively) water extract exhibited mild anti-plasmodial activity. The rest of the extracts did not exhibit any anti-plasmodial activity. Although the leishmanicidal activity of extracts were lower than for pentosam (80%), reasonable activity was observed for Aloe nyeriensis methanol (68.4+/-6.3%), Albizia coriara water (66.7+/-5.0%), Maytenus putterlickoides methanol (60.0+/-6.23%), Asparagus racemosus methanol and water (58.3+/-8.22 and 56.8+/-6.58%, respectively), Aloe nyeriensis water (53.3+/-5.1%) and Acacia tortilis water (52.9+/-6.55%) extracts at 1000 microg/ml. Leishmania major infected macrophages treated with methanol extracts of Suregada zanzibariensis and Aloe nyeriensis var kedongensis and pentostam had infection rates of 28+/-2.11, 30+/-1.22 and 40+/-3.69%, respectively at 1000 microg/ml, indicating better anti-leishmanial activity for the extracts. The methanol extract of Albizia coriara (44.0+/-3.69%) and aqueous extracts of Asparagus racemosus (42+/-3.84%) and Acacia tortilis (44+/-5.59%) had similar activity to pentosam. Multiplication indices for Leishmania major amastigotes treated with methanol extracts of Albizia coriaria, Suregada zanzibariensis and Aloe nyeriensis var kedongensis, aqueous extract of Acacia tortilis and pentosam were 28.5+/-1.43, 29.4+/-2.15, 31.1+/-2.22, 35.9+/-3.49 and 44.0+/-3.27%, respectively, at 1000 microg/ml, confirming better anti-leishmanial activity for the extracts. Aqueous extracts of Aloe nyeriensis (46.7+/-3.28%) and Albizia coriaria (47.5+/-3.21%) had similar activity level to pentosam. The plant extracts have better inhibitory activity while pentosam has better leishmanicidal activity. All extracts exhibited very low cytotoxicity (CC(50) > 500 microg/ml) against human embryonic lung fibroblast (HELF) cells. The investigations demonstrated the efficacy and safety of some extracts of plants that are used by rural indigenous communities for the treatment of parasitic diseases.

Anti-oxidative Effects of Rooibos Tea Extract on Autoxidation and Thermal Oxidation of Lipids.

J Oleo Sci. 2009; 58(6): 275-83Fukasawa R, Kanda A, Hara SPowdered rooibos tea extract (RTE), which is rich in polyphenols, is made from rooibos tea by freeze-drying. "Rooibos" is Afrikaans for "red bush," and the scientific name is "Aspalathus linearis." It is a broom-like member of the legume family of plants and is used to make an herbal tea which has been popular in South Africa for generations and is now consumed in many countries. In the present work, the anti-oxidative effect of RTE on oils and fats in autoxidation or thermal oxidation was studied, and it was confirmed that RTE has a very strong anti-oxidative effect on emulsifying oils owing to the water-soluble polyphenols such as rutin and quercetin contained in RTE. RTE was found to have a strong ability to quench radicals generated in the water phase, and to confer higher thermal stability against deep fat frying than tocopherol. But RTE showed little anti-oxidative effect on frying oil because of its lower oil-solubility.

Evaluation of the hepatotoxic and hepatoprotective effect of Rwandese herbal drugs on in vivo (guinea pigs barbiturate-induced sleeping time) and in vitro (rat precision-cut liver slices, PCLS) models

Exp Toxicol Pathol. 2009 Jun 1; Mukazayire MJ, Allaeys V, Buc Calderon P, Stévigny C, Bigendako MJ, Duez PPrecision-cut liver slices (PCLS) preserve the tissular organization of the organ and represent an in vitro model closer to in vivo conditions than hepatocytes cultures. As this may be an interesting tool not only for the investigation of hepatotoxic and protective effects but also for bioguided fractionations schemes, the usefulness of PCLS was compared with an in vivo test of liver function. Crude extracts derived from five herbs used in Rwanda for hepatoprotective activity were tested on CCl(4)-treated guinea pigs by the method of barbiturate-induced sleep modification. Aqueous extracts of Ocimum lamiifolium, Crassocephalum vitellinum, Guizotia scabra and Vernonia lasiopus leaves allowed animals to recover barbiturate sleep duration in proportions of 88%, 78%, 61% and 34%, respectively and Microglossa pyrifolia was found inactive. Dried methanolic extracts of the 5 plants were then tested in vitro on rat PCLS for protection against acetaminophen-induced hepatotoxicity. In this model, G. scabra, M. pyrifolia and V. lasiopus were found hepatotoxic by themselves and unable to prevent acetaminophen toxicity. The most active extract, obtained from O. lamiifolium, was subjected to bioassay-guided fractionation by chromatography on Si-C(18) to yield two quite active fractions. From a single animal, at least 50 PCLS explants can be prepared, which allows testing large amounts of samples, strengthening ethnopharmacological data on hepatoprotective medicinal plants and investigating hepatotoxic effects.