Rhodiola rosea 3% rosavin and 1% salidroside

Rhodiola rosea l., or golden root, is a popular plant in traditional medicine. In Eastern Europe and Asia, with a reputation for improving depression, enhancing work performance, eliminating fatigue and treating symptoms of asthenia subsequent to intense physical and psychological stress (Perfumi & Mattioli, 2006).*

Rhodiola rosea l. is one of the most popular adaptogenic and anti-stress plants in European and Asiatic traditional medicine. Its pharmacological properties appear to depend on its ability to modulate the activation of several components of the complex stress-response system. Exposure to both physical and psychological stress reduces feeding in rodents. A study was thus carried out to determine whether in rats an hydro alcoholic R. rosea extract standardized in 3% rosavin and 1% salidroside (RHO) reverses hypophagia induced by (1) physical stress due to 60 min immobilization; (2) intracerebroventricular injection of corticotrophin-­releasing factor (CRF, 0.2 μg/rat), the major mediator of stress responses in mammals; (3) intraperitoneal injection of Escherichia coli Lipopolysaccharide (LPS, 100 μg/kg); (4) intraperitoneal administration of fluoxetine (FLU, 8 mg/kg).*

The effect of the same doses of the plant extract was also tested in freely feeding and in 20 h food-­deprived rats. RHO was administered acutely by gavage to male Wistar rats 1 h before the experiments. The results showed that at 15 and 20 mg/kg, RHO reversed the anorectic effects induced both by immobilization and by intracerebroventricular CRF injection. Moreover, at the same doses, RHO failed to reduce the anorectic effect induced both by LPS and FLU, and did not modify food intake in both freely feeding and food-deprived rats. These findings strongly demonstrated that RHO is able selectively to attenuate stress-induced anorexia, providing functional evidence of claimed adaptogenic and anti-stress properties of Rhodiola rosea L (Titomanlio et al, 2013).*

Rhodiola may also play a role in fighting depression. In a group of 128 adult patients with depression and neurasthenia (a condition of fatigue, weakness, and inability to recover by resting), treatment with rhodiola extract three times a day significantly reduced or eliminated symptoms in 64% of the subjects. Among a group of patients hospitalized for depression, the addition of rhodiola to a treatment regimen of tricyclic antidepressants reduced the length of hospital stays and improved the patients' moods, thought processes, and motor activity.*

Even better, the herb not only reduced troublesome side effects of the antidepressants, but also proved to be effective in treating less severe forms of depression without other medications. Therapy of aesthetic conditions: clinical perspectives of application of Rhodiola rosea extract (golden root) (Brichenko, 1970).*

Magnolia Officinalis: Magnolol and Honokiol

Honokiol, a neolignane derivative of Magnolia bark, has central depressant action and, at much lower doses, anxiolytic activity. Results suggest that, in contrast with diazepam, honokiol selectively induces an anxiolytic effect with less liability of eliciting motor dysfunction and sedation or disinhibition. (Kuribara et al, 1998).*

An improved elevated plus-maze test in mice revealed that seven daily treatments with two different traditional Chinese medicines, known as Kampo medicines in Japan, Hange-­koboku-­to (composed of extracts of 5 plants) and Saiboku-­to (composed of extracts of 10 plants), produced an anxiolytic effect, and the effect was mainly due to the presence of honokiol derived from magnolia. These results confirm that honokiol derived from magnolia is the causal chemical of the anxiolytic effect of Chinese medicine formulas (Kuribara et al, 2000).*

The bark of the root and stem of various Magnolia species has been used in Traditional Chinese Medicine to treat a variety of disorders including anxiety and nervous disturbances. The biphenolic compounds honokiol (H) and magnolol (M), the main components of the Chinese medicinal plant Magnolia officinalis, interact with GABA-­A receptors in rat brain in vitro. The potentiation of GABAergic neurotransmission by H and M is probably involved in their previously reported anxiolytic and central depressant effects (Squires et al, 1999).*

Chinese herbs are widely used as important remedies in Oriental integrative medicine. Magnolol is a small polyphenolic molecule with low toxicity that is isolated from the herb genus Magnolia. In preclinical experiments, magnolol was found to have anti-oxidative, anti-inflammatory, anti-tumorigenic, anti-diabetic, anti-microbial, anti-neurodegenerative and antidepressant properties. Magnolol can also effectively regulate pain control, hormonal signalling, gastrointestinal and uterus modulation as well as provide cardiovascular and liver protective effects. The major biological mechanisms of action and potential health benefits of magnolol are described.*

These health benefits of magnolol have provided an increased interest in bringing this herbal compound to the clinic as a novel therapeutic agent. Knowledge of the multiple activities of magnolol can assist with the development of magnolol derivatives and the design of clinical trials that will maximize the potential benefit of magnolol in the patient setting (Chen et al, 2011).*

Myalgia Pain & Health

Musculoskeletal disorders comprise one of the most common and costly health problems in Europe and North America today. According to a survey conducted by the European Commission in 1999, about a third of all workers suffer from backache. The number of musculoskeletal disorders in the US increased fourfold between 1987 and 1992 and, today, the costs are estimated to exceed 65 billion dollars annually. A recent investigation in the Nordic countries shows that the costs associated with musculoskeletal diseases (absenteeism, early retirement, medical treatment and rehabilitation) account for between three and five percent of the gross national product.*

Studies report an association between psychosocial factors at the work place and musculoskeletal disorders. Time pressure, lack of influence over one's work and constant involvement in repetitive tasks of short duration often characterise jobs associated with a high risk for muscular problems (Bammer, 1990; Bongers et al., 1993; Haldeman, 1991; Johansson, 1994; Moon & Sauter, 1996; Tellnes, 1989; Lundberg, Elfsberg Dohns et al., 1999)*

A series of real life studies (Lundberg et al., 1989, 1997; Frankenhaeuser et al., 1989; Melin & Lundberg, 1997) shows that epinephrine output at work is significantly elevated among both blue and white collar workers, whereas norepinephrine levels are elevated in blue collar workers only. This is likely to reflect the fact that epinephrine is influenced mainly by mental stress and norepinephrine by physical demands.*

Asthma as well as anxiety improved by the Kampo extract Saiboku-to (Magnolol)

Asuka Naito, Hiroaki Satoh, and Kiyohisa Sekizawa. European Journal of Internal Medicine Volume 16, Issue 8, December 2005, Page 621

Anti-inflammatory and analgesic effects of magnolol

Wang JP1, Hsu MF, Raung SL, Chen CC, Kuo JS, Teng CM. Naunyn Schmiedebergs Arch Pharmacol. 1992 Dec;346(6):707-12.

Magnolol, isolated from Magnolia officinalis, inhibited mouse hind-paw oedema induced by carrageenan, compound 4880, polymyxin B and reversed passive Arthus reaction. Acetic acid-induced writhing response was depressed by magnolol, indomethacin and ibuprofen. The lethality of endotoxin challenge was reduced by pre-treatment with magnolol, indomethacin and BW755C, a dual cyclo-oxygenase/lipoxygenase inhibitor. The recovered myeloperoxidase activity in oedematous paw was significantly decreased in mice pre-treated with magnolol and BW755C. Suppression of oedema was demonstrated not only in normal mice but also in adrenalectomized animals. Magnolol was less potent on reducing PGD2 formation in rat mast cell than that of indomethacin. Unlike dexamethasone, magnolol did not increase liver glycogen level. The results suggest that the anti-inflammatory effect of magnolol was neither mediated by glucocorticoid activity nor through releasing steroid hormones from adrenal gland. The action of magnolol is proposed to be dependent on reducing the level of eicosanoid mediators.*

Anorexia

Rhodiola rosea L. extract reduces stress- and CRF-induced anorexia in rats

Mattioli L1, Perfumi M. J Psychopharmacol. 2007 Sep;21(7):742-50.

Rhodiola rosea l. is one of the most popular adaptogenic and anti-stress plants in European and Asiatic traditional medicine. Its pharmacological properties appear to depend on its ability to modulate the activation of several components of the complex stress-response system. Exposure to both physical and psychological stress reduces feeding in rodents. The aim of this work was thus to determine whether in rats an hydro alcoholic R. rosea extract standardized in 3% rosavin and 1% salidroside (RHO) reverses hypophagia induced by (1) physical stress due to 60 min immobilization; (2) intracerebroventricular injection of corticotrophin-releasing factor (CRF, 0.2 µg/rat), the major mediator of stress responses in mammals; (3) intraperitoneal injection of Escherichia coli Lipopolysaccharide (LPS, 100 µg/kg); (4) intraperitoneal administration of fluoxetine (FLU, 8 mg/kg). The effect of the same doses of the plant extract was also tested in freely feeding and in 20 h food-deprived rats. RHO was administered acutely by gavage to male Wistar rats 1 h before the experiments. The results show that at 15 and 20 mg/kg, RHO reversed the anorectic effects induced both by immobilization and by intracerebroventricular CRF injection. Moreover, at the same doses, RHO failed to reduce the anorectic effect induced both by LPS and FLU, and did not modify food intake in both freely feeding and food-deprived rats. These findings strongly demonstrated that RHO is able selectively to attenuate stress-induced anorexia, providing functional evidence of claimed adaptogenic and anti-stress properties of Rhodiola rosea L.*

Depression

Rhodiola may play a role in fighting depression. In a group of 128 adult patients with depression and neurasthenia (a condition of fatigue, weakness, and inability to recover by resting), treatment with rhodiola extract three times a day significantly reduced or eliminated symptoms in 64% of the subjects (Krasik et al., 1970). Among a group of patients hospitalized for depression, the addition of rhodiola to a treatment regimen of tricyclic antidepressants reduced the length of hospital stays and improved the patients' moods, thought processes, and motor activity. Even better, the herb not only reduced troublesome side effects of the antidepressants, but also proved to be effective in treating less severe forms of depression without other medications (Brichenko et al., 1986).*

Arrhythmias

Studies have also demonstrated heart-healthy properties of rhodiola. An eight-day trial of rhodiola extract increased the resistance of experimental animals to drug-induced arrhythmias (Lishmanov et al., 1993). The researchers believe that this anti-arrhythmic effect is associated with the herb's induction of opioid peptide biosynthesis. Another study found that rhodiola prevented stress-induced cardiac damage and catecholamine release from the heart muscle (Maslova et al., 1994).*

Magnolol: A multifunctional compound isolated from the Chinese medicinal plant Magnolia officinalis

Chen Y-H, Huang P-H, Lin F-y, et al. European Journal of Integrative Medicine. 2011 doi:10.1016/j.eujim.2011.09.002

Chinese herbs are widely used as important remedies in Oriental integrative medicine. Magnolol is a small polyphenolic molecule with low toxicity that is isolated from the herb genus Magnolia. In preclinical experiments, magnolol was found to have anti-oxidative, anti-inflammatory, anti-tumorigenic, anti-diabetic, anti-microbial, anti-neurodegenerative and anti-depressant properties. Magnolol can also effectively regulate pain control, hormonal signalling, gastrointestinal and uterus modulation as well as provide cardiovascular and liver protective effects.*

Chen et al briefly conducted PubMed and MEDLINE database reviews for articles that related to magnolol. The major biological mechanisms of action and potential health benefits of magnolol are described. These health benefits of magnolol have provided an increased interest in bringing this herbal compound to the clinic as a novel therapeutic agent. Knowledge of the multiple activities of magnolol can assist with the development of magnolol derivatives and the design of clinical trials that will maximize the potential benefit of magnolol in the patient setting.*

Honokiol - Activation of tumor suppressor LKB1 by abrogates cancer stem-like phenotype in breast cancer via inhibition of oncogenic Stat3

Sengupta S, Nagalingam A, Muniraj N et al. Oncogene (2017) 36, 5709–5721; doi:10.1038/onc. 2017.164

Tumor suppressor and upstream master kinase Liver kinase B1 (LKB1) plays a significant role in suppressing cancer growth and metastatic progression. Sengupta et al., (2017) show that low-LKB1 expression significantly correlates with poor survival outcome in breast cancer. In line with this observation, loss-of-LKB1 rendered breast cancer cells highly migratory and invasive, attaining cancer stem cell-like phenotype. Honokiol (HNK), a bioactive molecule from Magnolia grandiflora increased LKB1 expression, inhibited individual cell-motility and abrogated the stem-like phenotype of breast cancer cells by reducing the formation of mammosphere, expression of pluripotency-factors and aldehyde dehydrogenase activity. LKB1, and its substrate, AMP- dependent protein kinase (AMPK) are important for HNK-mediated inhibition of pluripotency factor. Results present the first in vitro and in vivo evidence to support crosstalk between LKB1, Stat3 and pluripotency factors in breast cancer and effective anticancer modulation of this axis with HNK treatment.*

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