WO2012156970A1 - Huile de graines de salvia sclarea pour utilisation dans le traitement de maladies cardiovasculaires ou de troubles anxieux - Google Patents

Huile de graines de salvia sclarea pour utilisation dans le traitement de maladies cardiovasculaires ou de troubles anxieux Download PDF

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Publication number
WO2012156970A1
WO2012156970A1 PCT/IL2012/050155 IL2012050155W WO2012156970A1 WO 2012156970 A1 WO2012156970 A1 WO 2012156970A1 IL 2012050155 W IL2012050155 W IL 2012050155W WO 2012156970 A1 WO2012156970 A1 WO 2012156970A1
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subject
disorder
lipid lowering
lowering drug
anxiety
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PCT/IL2012/050155
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English (en)
Inventor
Samuel Edelstein
Lior YEHEZKELY
Yaron YEHEZKELY
Shay SEGAL
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Magnetika Interactive Ltd.
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Publication of WO2012156970A1 publication Critical patent/WO2012156970A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to compositions comprising salvia sclarea oil.
  • Heart disease or cardiovascular disease is a class of diseases that involve the heart and/or blood vessels.
  • Cardiovascular disease is usually related to atherosclerosis (a condition in which an artery wall thickens as the result of a build-up of fatty materials such as cholesterol) and is considered to be the world's largest killer, claiming around 17 million lives a year according to world health organization reports.
  • Atherosclerosis and the subsequent cardiovascular disease are typically the biggest killers in western societies. While the detailed mechanisms of atherosclerosis are not completely understood, much is now known about the complex causes of the atherosclerosis process.
  • Atherosclerosis apparently begins when the inner lumen endothelium becomes damaged by oxidized low-density lipoprotein (LDL) cholesterol (so-called "bad cholesterol), infectious agents, hyperglycemia, homocystine, and/or oxidative toxins. Oxidized LDL cholesterol begins accumulating in the damaged vascular endothelial cells, leading to fatty streaks, vascular inflammation, and smooth muscle cell proliferation.
  • LDL low-density lipoprotein
  • Triglycerides may also contribute to thickening of artery walls, a physical change believed to be a predictor of atherosclerosis.
  • statins block the pathway for synthesizing cholesterol in the liver.
  • Statins significantly reduce serum cholesterol and LDL-serum levels, and slow progression of coronary atherosclerosis.
  • statins can lower LDL cholesterol by 1.8 mmol/L (70 mg/dl), which translates into a 60% decrease in the number of cardiac events (heart attack, sudden cardiac death) and a 17% reduced risk of stroke after long-term treatment.
  • statins have less effect (than for example fibrates or niacin) in reducing triglycerides and raising HDL- cholesterol ("good cholesterol").
  • CVD cardiovascular diseases
  • diseases/disorders associated therewith in which the use of lipid lowering drugs will be accompanied with the sought-after increase in HDL serum levels and/or with a concomitant reduction in serum triglyceride and LDL-cholesterol levels.
  • agents that can reduce the undesirable adverse effects associated with the treatment of lipid lowering drugs and in particular with statins are also a need for agents that can reduce the undesirable adverse effects associated with the treatment of lipid lowering drugs and in particular with statins.
  • lipid lowering drugs or combinations thereof are often contraindicated or vary in effectiveness in different people, making it a complex exercise for physicians to prescribe the right combination of lipid lowering drugs for subjects who require higher doses of lipid lowering drugs such as LDL-cholesterol lowering drugs.
  • prescribing a statin based pharmaceutical in combination with an additional LDL-cholesterol lowering drug may not be favorable due to the added adverse effects of the additional drug and also because of the extra burden the added agent may have on renal and/or hepatic elimination of the combined drugs.
  • CVD cardiovascular disease
  • the present invention provides a method of improving the lipid profile in a subject, comprising administering to the subject an effective amount of salvia sclarea seed oil extract.
  • the present invention provides a method of improving the serum lipid profile in a subject being treated with at least one lipid lowering drug, comprising administering to a subject an effective amount of salvia sclarea seed oil extract.
  • the term "improving the serum lipid profile” refers to a decrease in serum LDL and/or triglycerides and/or total serum cholesterol levels and/or an increase in serum HDL levels (or any combination thereof) in a subject.
  • the 'improvement in the serum lipid profile' is defined as greater than the improvement in the serum lipid profile obtained following treatment with the at least one lipid lowering drug alone.
  • the improvement of serum lipid profiles includes one or more of reduction in total serum cholesterol level, reduction in serum LDL-cholesterol levels; increase in serum HDL-cholesterol levels; and/or reduction in serum triglyceride levels.
  • the method of the invention is employed for bringing about a reduction in the total cholesterol level in the serum of said subject.
  • the method of the invention is employed for bringing about a reduction in the LDL-cholesterol levels in the serum of said subject.
  • the method of the invention is employed for bringing about an increase in the HDL- cholesterol levels in the serum of said subject.
  • the method of the invention is employed for bringing about a reduction in the triglyceride levels in the serum of said subject.
  • lipid lowering drug refers to a drug which administration to a subject results in any one of the following outcomes or any combination thereof: reduction in total serum cholesterol level, reduction in serum LDL-cholesterol levels; increase in serum HDL-cholesterol levels; reduction in serum triglyceride levels.
  • lipid lowering drugs include statins, fibrates, niacin, bile acid sequestrants (resins), ezetimibe, phytosterols, Orlistat and Acipimox (a niacin derivative).
  • the lipid lowering drug is a statin.
  • statin refers to any statin known in the art (being a HMG-CoA reductase inhibitor) which acts to decrease LDL-cholesterol blood/tissue levels and/or have beneficial effects that may also improve CVD.
  • statins which may be used in the context of the present invention include one or more of atorvastatin, cerivastatin, fluvastatin, mevastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin.
  • said statin is atorvastatin.
  • said statin is cerivastatin.
  • said statin is fluvastatin.
  • said statin is mevastatin.
  • said statin is lovastatin.
  • said statin is pravastatin.
  • said statin is rosuvastatin.
  • said statin is simvastatin.
  • the "salvia sclarea seed oil extract” refers to oil extracted from the whole seed of salvia sclarea essentially in an unprocessed form as separated from the full plant.
  • the Salvia sclarea seed oil may be in an essentially pure form, i.e. being essentially free from other components, or as a mixture with other seed components.
  • the oil may be obtained by various manners known to separate oil from plant seeds without damaging their nutritional value.
  • the subject being treated according to any one method according to the present invention or being treated by a composition according to the present invention is a subject having a cardiovascular disease and/or a disease or disorder associated therewith, or a subject having predisposition for suffering from such a disease.
  • cardiovascular disease and/or a disease or disorder associated therewith refers to any disease or disorder in any of the various parts of the cardiovascular system, which consists of the heart and all of the blood vessels found throughout the body.
  • diseases/disorders of the heart may include coronary artery disease, coronary heart disease, cardiomyopathy, valvular heart disease, pericardial disease, congenital heart disease (e.g., coarctation, atrial or ventricular septal defects), and heart failure.
  • Diseases/disorders of the blood vessels may include arteriosclerosis, atherosclerosis, stroke, hypertension, aneurysm, peripheral arterial disease, varicose veins, vasculitis, intermittent claudication, venous incompetence, venous thrombosis and lymphedema.
  • CVD patients may be individuals who have established cardiovascular disease with or without a prior myocardial infarction (e.g. subjects medically diagnosed as having coronary artery disease) and also individuals having a genetic predisposition to CVD (e.g. subjects with a family history of CVD) which demonstrate at least some symptoms of CVD or symptoms of diseases/disorders associated therewith.
  • the present invention provides a method for reducing at least one lipid lowering drug side-effect in a subject treated with at least one lipid lowering drug, comprising administering to a subject an effective amount of salvia sclarea seed oil extract.
  • lipid lowering drug side-effect refers to any side- effect associated with treatment with a lipid lowering drug, as defined herein, that is known from the pertinent field of the art.
  • Some non-limiting examples of such side effects include: muscle pain (myalgia) and rhabdomyolysis, muscle weakness and neuropathy, memory loss, headache, abdominal pain, asthenia (general feeling of weakness), constipation, diarrhea, dyspepsia, flatulence, nausea, upper respiratory infections, liver damage (raised liver enzymes) and rash or flushing.
  • the subject may be an individual having cardiovascular disease and/or a disease or disorder associated therewith that is not receiving any medical treatment (e.g. with a lipid lowering drug).
  • the subject is an individual that is receiving treatment to treat CVD or any of its symptoms (e.g. a patient receiving treatment with various drugs used to treat CVD and/or drugs used to treat diseases/disorders associated therewith other than lipid lowering drugs).
  • the subject is a subject not diagnosed as having CVD or a disease/disorder associated therewith.
  • the at least one lipid lowering drug and said oil extract component may be administrated to the subject simultaneously, sequentially or separately.
  • the present invention provides a combination comprising an effective amount of at least one lipid lowering drug and an effective amount of salvia sclarea seed oil extract.
  • said combination is effective for improving the lipid profile in a subject treated with the at least one lipid lowering drug.
  • the combination as defined herein, may comprise the at least one lipid lowering drug and extract components as separate dosage forms or in a single composition to enable the components of the combination to be administered simultaneously, sequentially or separately.
  • the "combination" may be either simultaneously, sequentially or separately administered to the subject wherein the at least one lipid lowering drug and extract components of the combination are administered either simultaneously (as separate dosage forms or in a single composition), sequentially (one component followed immediately, e.g. seconds or minutes, after the other), or separated by a suitable time interval (e.g. administration of the extract hours, days or even weeks after initiating treatment with the lipid lowering drug).
  • a suitable time interval e.g. administration of the extract hours, days or even weeks after initiating treatment with the lipid lowering drug.
  • each component e.g. lipid lowering drug, extract
  • each component may be administered in the same form or a different form (e.g. oral, parenteral).
  • the components of the combination may also be provided in a kit form wherein the kit is preferably in compartmentalized form adapted for the separate administration of the components.
  • the components of the combination are administered simultaneously.
  • the components may be provided as a single composition containing the two or more components or may also be provided in a kit form, wherein the kit is compartmentalized for the simultaneous administration of the components.
  • the composition may optionally comprise one or more pharmaceutically acceptable carriers, diluents or excipients, which are pharmaceutically acceptable in the sense of being compatible with the other ingredients of the composition and not injurious to the subject, as recognized by the skilled artesian.
  • the present invention also provides a combination comprising an effective amount of at least one lipid lowering drug and an effective amount of salvia sclarea seed oil extract for reducing at least one lipid lowering drug side-effect in a subject treated with at least one lipid lowering drug.
  • the present invention provides the use of a combination, as defined herein, in the preparation of a medicament for improving the lipid profile in a subject treated with the at least one lipid lowering drug.
  • the present invention provides the use of a combination, as defined herein, in the preparation of a medicament for reducing at least one lipid lowering drug side-effect in a subject treated with at least one lipid lowering drug.
  • the present invention provides a composition comprising an effective amount of salvia sclarea seed oil extract for improving the lipid profile in a subject.
  • the subject is a subject having cardiovascular disease or a disease/disorder associated therewith.
  • the present invention also contemplates the use of a composition, as defined herein, in the preparation of a medicament for improving the serum lipid profile in a subject treated with at least one lipid lowering drug.
  • the present invention provides a combination, as defined herein, for improving the lipid profile in a subject treated with the at least one lipid lowering drug. In still another one of its aspects the present invention provides a combination, as defined herein, for reducing at least one lipid lowering drug side-effect in a subject treated with at least one lipid lowering drug.
  • Salvia sclarea seed oil in the preparation of a composition for treating anxiety or mood disorder.
  • composition comprising Salvia sclarea seed oil, said composition having anxiolytic effect.
  • a method of treating or preventing anxiety or mood disorders comprising administering to a subject in need thereof Salvia sclarea seed oil or a composition comprising an effective amount of said oil.
  • anxiety disorder and “mood disorder” generally refer to abnormal, pathological anxiety, fears, and phobias that are generally experienced by an individual for an extensive period of time, which may or may not be directly associated with states such as stress, anxiety, etc.
  • anxiety disorders include generalized anxiety disorder, panic disorder, specific phobias, social anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, separation anxiety.
  • mood disorders include mania, dysphoria, major depression disorder (i.e., unipolar disorder), bipolar disorder, dysthymia, cyclothymia and other mood disorders (see, e.g. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM IV».
  • OCD obsessive compulsive disorder
  • major depression disorder' or '"unipolar disorder refer to a mood disorder involving any of the following symptoms feelings of hopelessness, pessimism, worthlessness or guilt; persistent sad, anxious, or “empty” mood; or helplessness; thoughts of death or suicide or suicide attempts; insomnia, early- morning awakening, or oversleeping; loss of interest or pleasure in hobbies and activities that were enjoyed in the past, including sex; decreased energy, fatigue, being “slowed down”; difficulty concentrating, remembering, or making decisions; appetite and/or weight loss or overeating and weight gain; restlessness or irritability, or persistent physical symptoms that do not respond to treatment, such as headaches digestive disorders, and chronic pain.
  • bipolar disorder refers to a mood disorder characterized by alternating periods of extreme moods, A person with bipolar disorder experiences cycling of moods that usually swing between overly elated or irritable (mania) to sad and hopeless (depression) and then back again, with periods of normal mood in between.
  • Bipolar disorders include bipolar disorder I (mania with or without major depression) and bipolar disorder II (hypomania with major depression).
  • composition of the invention for treating or preventing anxiety or mood disorder is regarded anxiolytic.
  • the term refers to the Salvia sclarea seed oil or composition comprising same when used to treat e.g., symptoms of anxiety or mood disorders, including stress, anxiety, neuroses, and obsessive fears, as defined herein.
  • the subject to be treated by the anxiolytic composition of the invention is one who has been diagnosed with or is suspected of having an anxiety or mood disorder characterized, e.g. by stresse, anxiety, neuroses, or obsessive fears, as defined herein.
  • the subject may be suffering from an anxiety or mood disorder at the time of treatment onset or who is at risk (has predisposition) of developing anxiety or mood disorder.
  • compositions, combinations or formulations according to the present invention comprise an amount of the Salvia sclarea seed oil which is effective to achieve the desired therapeutic effect as described herein.
  • the "effective amount” for purposes described herein is determined by such considerations as may be known in the art. The amount must be effective to achieve the desired therapeutic effect as described herein, namely to lower total serum cholesterol, lower serum LDL and/or triglyceride levels and/or increase serum HDL-cholesterol levels, or treating one or more of the anxiety and mood disorders, depending, inter alia, on the type and severity of the disease to be treated and the treatment regime.
  • the effective amount is typically determined in appropriately designed clinical trials (dose range studies) and the person versed in the art will know how to properly conduct such trials in order to determine the effective amount. As generally known, an effective amount depends on a variety of factors such as half life in the body, on undesired side effects, if any, on factors such as age and gender, etc.
  • treatment refers to the administering of a therapeutic amount of the Salvia sclarea seed oil, as defined herein, which is effective to ameliorate undesired symptoms associated with a particular disease, to prevent the manifestation of such symptoms before they occur, to slow down the progression of the disease (as may be evident from various diagnostic procedures known to the skilled artesian), slow down the deterioration of symptoms, to enhance the onset of remission period, slow down the irreversible damage caused in the progressive chronic stage of the disease, to delay the onset of said progressive stage, to lessen the severity or cure the disease, to improve survival rate or more rapid recovery, or to prevent the disease from occurring or a combination of two or more of the above.
  • Fig. 1 provides HDL (mg/dl): individual patient changes from baseline to month 3.
  • Figs. 2 provide triglycerides (mg/dl): individual patient changes from baseline to month 3.
  • Fig. 3 provides LDL (mg/dl): individual patient changes from baseline to month 3.
  • Fig. 4 provides cholesterol (mg/dl): individual patient changes from baseline to month 3.
  • Figs. 5A-C depict Group 1 animals' behavior in the dominant-submissive relationships (DSR) test: Fig. 5A- DSR of submissive mice; Fig. 5B- DSR of dominant mice; Fig. 5C- DSR of dominant and submissive mice combined.
  • DSR dominant-submissive relationships
  • Figs. 6A-C depict Group 2 animals' behavior in the dominant-submissive relationships (DSR) test: Fig. 6A- DSR of submissive mice; Fig. 6B- DSR of dominant mice; Fig. 6C- DSR of dominant and submissive mice combined.
  • Figs. 7A-B depict Group 1 animals behavior in the open field test: Fig. 7A- open field- crossing; Fig. 7B- open filed- rearing.
  • Figs. 8A-B depict Group 2 animals behavior in the open field test: Fig. 8A- open field- crossing; Fig. 8B- open filed- rearing.
  • Figs. 9A-C depict Group 1 animals' behavior in the elevated plus maze (EPM): Fig. 9A- EPM- total entries; Fig. 9B- EPM- open time/total time; Fig. 9C- EPM- open entries/total entries.
  • EPM elevated plus maze
  • Figs. lOA-C depict Group 2 animals' behavior in the elevated plus maze (EPM): Fig. 10A - EPM- total entries; Fig. 10B - EPM- open time/total time; Fig. IOC - EPM- open entries/total entries.
  • EPM elevated plus maze
  • Figs. 11A-B shows animals' corticosterone levels; Fig. 11A - blood corticosterone Group 1 ; Fig. 11B - blood corticosterone Group 2.
  • the extract as defined herein, was prepared as described in [1]. Briefly, salvia sclarea seed oil was extracted from salvia seeds by a multi-stage press-extractor. Prior to extraction the seeds were lightly heated and wetted for maximum yields. The excess water was then removed by a decanting centrifuge.
  • the extract contained 50% omega 3 alpha-linolenic acid (ALA), as well as phytosterols, coenzyme- Q10, vitamin E and phytoprostans (non-enzymatically produced prostaglandin-like compounds).
  • ALA omega 3 alpha-linolenic acid
  • phytosterols phytosterols
  • coenzyme- Q10 phytosterols
  • vitamin E phytoprostans
  • mice used in this study were descendants of the Sabra line originally developed at the Hebrew University and were selectively bred for ten generations at the Ariel University Center on basis of their behavior in the DSR test. Animals were given their specifically designed rodent chow and water ad libitum. During DSR testing, chow was provided according to the DSR protocol. The colony room was maintained on a 12h L: 12h D cycle (lights on 07.00-19.00 h). The experiments were conducted in compliance with the NIH/USDA guidelines, under the approved Institutional Animal Care and Use Committee.
  • the animals were divided into two experimental groups:
  • Group 1 Forty males began to receive Salvia or Sunflower oil at the age of 24 days immediately after weaning and up to the end of the experiment.
  • Group 2 Pregnant females were fed with Salvia oil or Sunflower oil fortified chow from day 1 of pregnancy. After their delivery, they and their offspring continued to receive Salvia or Sunflower oil fortified chow. At the age of 24 days male offspring were weaned and continued to receive the Salvia or Sunflower oil up to the end of the experiment. Group 2 consisted of:
  • the DSR paradigm was performed as previously described.
  • the apparatus made from Plexiglas, consists of two identical chambers (12x8.5x7 cm) joined by a tunnel (2.5x2.5x27 cm). A 0.5 cm diameter hole was cut in the bottom center of the tunnel.
  • a self -refilling feeder is connected to the tunnel, allowing a constant supply of sweetened milk (3% fat, 10% sugar).
  • the tunnel has narrow slits cut on both sides of the feeder for easy gate insertion and removal. In this way, the paired mice have an equal time starting position at the beginning of each session.
  • DSR tests were carried out on five consecutive days per week. During each 16 h period preceding testing, the mice were deprived of food, but water was provided ad libitum. The animals had free access to food for two days between testing periods until the night before the next five day testing period. The animals were housed in groups of five per home cage. Pairs of SUB mice from different home cages were matched for relatively similar weight and were tested against each other according to the DSR protocol daily. During each 5 minute DSR session, milk drinking times were recorded manually by human observer.
  • the EPM test was used to assess anxiety-like behavior.
  • the apparatus comprised of two enclosed (10x45x40 cm) and two open (10x45 cm) arms that extend from a common central platform (10x10 cm).
  • the black wooden apparatus was elevated on a wooden box to a height of 60 cm above floor level.
  • the tests were conducted during the period of illumination in the mice's colony room. For better habituation, all animals were placed in the experimental room one hour prior to the test. Each animal was placed at the center of the maze, facing one of the enclosed arms.
  • Each mouse spent a 5 minute session in the EPM, during which the number of entries into open and closed arms, as well as time spent in the open and closed arms were manually scored. Between each mouse's session, the maze was carefully cleaned with tissue paper wet with a 75% ethanol solution.
  • Open field (OF) Open field
  • the OF test was used to estimate spontaneous locomotor (horizontal) and exploratory (vertical) activity.
  • the OF apparatus consisted of a clear glass box (30x40 cm) which floor was divided by lines drawn into 20 equally sized squares. Each mouse was placed individually in the center of the apparatus. Horizontal (number of squares crossed) and vertical (number of rearings) activity was recorded manually for 6 min. Between subjects, the apparatus was thoroughly washed with water and dried with tissue paper.
  • the animals were measured weekly using an electronic analytic scale. The results during DSR testing were excluded from calculations due to the influence of the DSR feeding schedule upon eating and weight.
  • Salvia or Sunflower treated mice's behavioral and corticosterone parameters were fitted by GraphPad Prism software. Statistical significance of difference between Salvia and Sunflower treated mice was evaluated using One- and Two-Way ANOVA with Bonferroni-corrected post-hoc, as well as i-test analysis depending on experimental set up.
  • the EPM test was used to assess anxiety-like behavior. The number of entries to the open and closed arms, and the time spent there, were recorded. As seen in DSR and open field tests, Group 1 showed no differences between the Salvia and Sunflower groups' exploratory activity (Fig. 9). Among Group 2, the Total Entries and the Open Time/Total Time index showed no differences between Salvia and Sunflower groups (Figs. 10A and 10B), while the Open Entries/Total Entries index of dominant animals who received Salvia oil fortified food was significantly (p ⁇ 0.01) higher (Fig. IOC). No differences were observed in exploratory activity among the submissive animals.
  • Group 1 showed no differences in corticosterone levels based upon Salvia or Sunflower supplementation (Fig. 11A).
  • Fig. 11B it was found that submissive animals fed Salvia oil-fortified feed had significantly (p ⁇ 0.05) lower corticosterone levels than their submissive counterparts (Fig. 11B). No differences were observed in corticosterone levels of the dominant animals.
  • the invention disclosed herein demonstrates that chronic salvia oil supplementation is efficient in mood stabilizing and anxiolytic effects.
  • Salvia oil significantly weakened the behavioral phenotype of dominant Sabra mice.
  • Previous studies have validated the use of the DSR model as an animal model of mood disorder, in which submissiveness represents depressive-like behavior and dominance represents manic-like behavior, and clinical antidepressants and mood-stabilizing drugs reduce submissive and dominant behavior, respectively.
  • the reduction of dominant behavior of Salvia oil treated dominant mice therefore may be explained as a mood-stabilizing effect of Salvia oil treatment.
  • the lack of effects upon of submissive mice in the DSR test may point to a selective mood stabilizing action of Salvia oil treatment upon manic-like dominant animals.
  • the calming effect of Salvia oil upon dominant animals in the DSR model was correlated with its anxiolytic effect upon the same animals in the EPM test.
  • the Open Entries/Total Entries ratio of dominant animals who received Salvia oil was significantly (p ⁇ 0.01) higher than of those who received Sunflower oil (Fig. 10).
  • a broad range of antidepressant and anxiolytic compounds have been shown to increase spontaneous locomotion in the Open Field test, of which vertical movement is considered to be more sensitive than horizontal movement to pharmacological treatment.
  • the higher rearing scores of the Salvia oil treated dominant mice may be a nascent expression of the anxiolytic effects of Salvia oil upon these animals representing manic-like behavior.

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Abstract

L'invention concerne des compositions utilisables en médecine comprenant de l'huile de graines de Salvia sclarea. Les compositions de la présente invention sont utilisées pour améliorer le profil lipidique d'un sujet et également dans le traitement et la prophylaxie de troubles anxieux ou de troubles de l'humeur.
PCT/IL2012/050155 2011-05-04 2012-05-03 Huile de graines de salvia sclarea pour utilisation dans le traitement de maladies cardiovasculaires ou de troubles anxieux WO2012156970A1 (fr)

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US11806316B2 (en) 2019-02-22 2023-11-07 Microphyt Food supplement
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11806316B2 (en) 2019-02-22 2023-11-07 Microphyt Food supplement
RU2809772C2 (ru) * 2019-02-22 2023-12-18 Микрофит Пищевая добавка

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