Lymphosarcoma

Description

Rhodiola rosea (also known as golden root and Arctic root) has been categorized as an adaptogen by Russian researchers due to its observed ability to increase resistance to a variety of chemical, biological, and physical stressors. It is a popular plant in traditional medical systems in Eastern Europe and Asia, with a reputation for stimulating the nervous system, improving depression, enhancing work performance, improving sleep, eliminating fatigue, and preventing high altitude sickness. (1)

Active constituents

Rhodiola species contain a range of antioxidant compounds, including p-tyrosol, organic acids (gallic acid, caffeic acid, and chlorogenic acid), and flavonoids (catechins and proanthocyanidins). (2,3)

The stimulating and adaptogenic properties of Rhodiola rosea are attributed to p-tyrosol, salidroside (synonym: rhodioloside and rhodosin), rhodioniside, rhodiolin, rosin, rosavin, rosarin, mad rosiridin. (1,4) Rosavin is the constituent currently selected for standardization of extracts. (5)

p-Tyrosol has been shown to be readily and dose-dependently absorbed after an oral dose; (6,7) however, pharmacokinetic data on the other adaptogenic compounds found in Rhodiola rosea is unavailable.

Mechanisms of Action

The adaptogenic properties, cardiopulmonary protective effects, and central nervous system activities of Rhodiola rosea have been attributed primarily to its ability to influence levels and activity of biogenic monoamines such as serotonin, dopamine, and norepinephrine in the cerebral cortex, brain stem, and hypothalamus. It is believed the changes in monoamine levels are due to inhibition of the activity of enzymes responsible for monoamine degradation and facilitation of neurotransmitter transport within the brain. (8)

In addition to these central effects, Rhodiola has been reported to prevent both catecholamine release and subsequent cyclic AMP elevation in the myocardium, and the depletion of adrenal catecholamines induced by acute stress. (9)

Rhodiola's adaptogenic activity might also be secondary to induction of opioid peptide biosynthesis and through the activation of both central and peripheral opioid receptors. (10-13)

Clinical Indications

Chronic Stress

In a physical endurance test, Rhodiola administration increased rat swimming time 135-159 percent. (14) When Rhodiola-treated rats were subjected to a four-hour period of non-specific stress, the expected elevation in beta-endorphin was either not observed or substantially decreased, leading researchers to the conclusion that the characteristic stress-induced perturbations of the hypothalamic-pituitary-adrenal axis can be decreased or totally prevented by Rhodiola supplementation. (10)

It is suggested that this plant has great utility as a therapy in asthenic conditions (decline in work performance, sleep disturbances, poor appetite, irritability, hypertension, headaches, and fatigue) developing subsequent to intense physical or intellectual strain, influenza and other viral exposures, and other illness. (15) Supplementation favorably influenced fatigue and mental performance in physicians during the first two weeks on night duty. (16)

Students receiving a standardized extract of Rhodiola rosea demonstrated significant improvements in physical fitness, psychomotor function, mental performance, and general well-being. Subjects receiving the Rhodiola extract also reported statistically significant reductions in mental fatigue, improved sleep patterns, a reduced need for sleep, greater mood stability, and a greater motivation to study. The average exam scores between students receiving the Rhodiola extract and placebo were 3.47 and 3.20, respectively. (17)

Cancer

All of the anticancer research on Rhodiola has been conducted in animal models. In these models, administration has resulted in inhibition of tumor growth and decreased metastasis in rats with transplanted solid Ehrlich adenocarcinoma and metastasizing rat Pliss lymphosarcoma (18) and transplanted Lewis lung carcinomas. (19)

Combining Rhodiola rosea extract with the anti-tumor agent cyclophosphamide in animal tumor models resulted in enhanced anti-tumor and anti-metastatic efficacy of drug treatment, as well as reduced drug-induced toxicity. (19) Animal experimental data notes the addition of Rhodiola rosea extract to a protocol with Adriamycin results in improved inhibition of tumor dissemination (as compared to that found with Adriamycin alone). The combined protocol also prevented liver toxicity. (20)

Side Effects and Toxicity

Clinical feedback indicates, at doses of 1.5-2.0 grams and above, Rhodiola rosea extract standardized for 2% rosavin might cause some individuals to experience an increase in irritability and insomnia within several days.

Evidence on the safety and appropriateness of Rhodiola rosea supplementation during pregnancy and lactation is currently unavailable.

Dosage

Dosage varies depending upon standardization. For chronic administration, a daily dose of 360-600 mg Rhodiola extract standardized for 1% rosavin, 180-300 mg of an extract standardized for 2% rosavin, or 100-170 mg of an extract standardized for 3.6% rosavin is suggested. Administration is normally begun several weeks prior to a period of expected increased physiological, chemical, or biological stress, and continued throughout the duration of the challenging event or activity.

When using Rhodiola rosea as a single dose for acute purposes (e.g., for an exam or athletic competition), the suggested dose is three times the dose used for chronic supplementation.

Rhodiola rosea has been administered for periods ranging from as little as one day (acute administration) up to four months. Until more specific information is available, a dosing regimen following the established patterns used with other plant adaptogens--with periodic intervals of abstinence --seems warranted when Rhodiola rosea is being used chronically.

References

(1.) Petkov VD, Yonkov D, Mosharoff A, et al. Effects of alcohol aqueous extract from Rhodiola rosea L. roots on learning and memory. Acta Physiol Pharmacol Bulg 1986;12:3-16.

(2.) Lee MW, Lee YA, Park HM, et al. Antioxidative phenolic compounds from the roots of Rhodiola sachalinensis A. Bor. Arch Pharm Res 2000;23:455-458.

(3.) Ohsugi M, Fan W, Hase K, et al. Active-oxygen scavenging activity of traditional nourishing-tonic herbal medicines and active constituents of Rhodiola sacra. J Ethnopharmacol 1999;67:111-119.

(4.) Linh PT, Kim YH, Hong SP, et al. Quantitative determination of salidroside and tyrosol from the underground part of Rhodiola rosea by high performance liquid chromatography. Arch Pharm Res 2000;23:349-352.

(5.) Boon-Niermeijer EK, van den Berg A, Wikman G, Wiegant FA. Phyto-adaptogens protect against environmental stress-induced death of embryos from the freshwater snail Lymnaea stagnalis. Phytomedicine 2000;7:389-399.

(6.) Visioli F, Galli C, Bornet F, et al. Olive oil phenolics are dose-dependently absorbed in humans. FEBS Lett 2000;468:159-160.

(7.) Bonanome A, Pagnan A, Caruso D, et al. Evidence of postprandial absorption of olive oil phenols in humans. Nutr Metab Cardiovasc Dis 2000;10:111-120.

(8.) Stancheva SL, Mosharrof A. Effect of the extract of Rhodiola rosea L. on the content of the brain biogenic monamines. Med Physiol 1987;40:85-87.

(9.) Maslova LV, Kondrat'ev BI, Maslov LN, Lishmanov IB. The cardioprotective and antiadrenergic activity of an extract of Rhodiola rosea in stress. Eksp Klin Farmakol 1994;57:61-63. [Article in Russian]

(10.) Lishmanov IB, Trifonova ZV, Tsibin AN, et al. Plasma beta-endorphin and stress hormones in stress and adaptation. Biull Eksp Biol Med 1987;103:422-424. [Article in Russian]

(11.) Lishmanov IB, Maslova LV, Maslov LN, Dan'shina EN. The anti-arrhythmia effect of Rhodiola rosea and its possible mechanism. Biull Eksp Biol Med 1993;116:175-176. [Article in Russian]

(12.) Maimeskulova LA, Maslov LN, Lishmanov IB, Krasnov EA. The participation of the mu-, delta- and kappa-opioid receptors in the realization of the anti-arrhythmia effect of Rhodiola rosea. Eksp Klin Farmakol 1997;60:38-39. [Article in Russian]

(13.) Lishmanov IB, Naumova AV, Afanas'ev SA, Maslov LN. Contribution of the opioid system to realization of inotropic effects of Rhodiola rosea extracts in ischemic and reperfusion heart damage in vitro. Eksp Klin Farmakol 1997;60:34-36. [Article in Russian]

(14.) Azizov AP, Seifulla RD. The effect of elton, leveton, fitoton and adapton on the work capacity of experimental animals. Eksp Klin Farmakol 1998;61:61-63. [Article in Russian]

(15.) Germano C, Ramazanov Z, Bernal Suarez M. Arctic Root (Rhodiola rosea): The Powerful New Ginseng Alternative. New York, NY: Kensington Publishing Corp; 1999.

(16.) Darbinyan V, Kteyan A, Panossian A, et al. Rhodiola rosea in stress induced fatigue--a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine 2000;7:365-371.

(17.) Spasov AA, Wikman GK, Mandrikov VB, et al. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine 2000;7:85-89.

(18.) Udintsev SN, Shakhov VP. The role of humoral factors of regenerating liver in the development of experimental tumors and the effect of Rhodiola rosea extract on this process. Neoplasma 1991;38:323-331.

(19.) Udintsev SN, Schakhov VP. Decrease of cyclophosphamide haematotoxicity by Rhodiola rosea root extract in mice with Ehrlich and Lewis transplantable tumors. Eur J Cancer 1991;27:1182.

(20.) Udintsev SN, Krylova SG, Fomina TI. The enhancement of the efficacy of adriamycin by using hepatoprotectors of plant origin in metastases of Ehrlich's adenocarcinoma to the liver in mice. Vopr Onkol 1992;38:1217-1222. [Article in Russian]

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