Herbs; Nature's Apothecary!

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Herbs; Nature's Apothecary!

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Herbs have been used as natural medicines since ancient times.
Modern 'science' has belatedly and reluctantly admitted to the medicinal efficacy of Herbs.
However as always it is their isolated and often artificially produced 'active ingredients' which are given credit for pharmacological properties.

Following is a selection of these active ingredients, or nutraceuticals / bioceuticals, of Herbs with prophylactic and therapeutic health benefits according to scientific studies:

♦ Rosmarinic Acid

• Rosmarinic Acid content in mg/g of selected herbs:[α][β]
Latin Name Common Names mg/g Picture
Melissa officinalis Lemon Balm, Melissa, Citronella 36.5 Image
Mentha aquatica Water Mint 24.6 Image
Mentha spicata Spearmint 58.5 Image
Rosmarinus officinalis Rosemary 7.2 Image
Salvia officinalis Sage 16.4 Image
Thymus vulgaris Thyme German/Garden Thyme 23.5 Image
Thymus citriodorus Lemon/Citrus Thyme 31.5 Image

♦ Scientific studies examining the therapeutic and prophylactic efficacy of Rosmarinic Acid for various Disorders:
  • Alzheimer prevention, Cognitive improvement [9]
  • Anti-viral properties [13]
  • Arthritis protective; Osteo-/Rheumatoid Arthritis [12]
  • Asthma protective [17]
  • Breast Cancer, prophylactic and therapeutic [20]
  • Cancer protective [16]
  • Diabetes therapeutic, Hyperglycemia prevention [18][19]
  • Gastric Ulcers [2]
  • Heart Attack protective [14]
  • Heart protective against toxins [7]
  • Hearing loss protective [11]
  • Hypertension/High Blood-pressure lowering [15]
  • Insomnia [21]
  • Kidney Disease [3]
  • Learning improvement & Senility prevention [6]
  • Liver Disease protective [1][3][8]
  • Lung protective [10]
  • Memory & Learning improvement [19]
  • Neuro-protective against toxin induced injury [5]
  • Testicular & Sperm injury protective from toxic agents [4]
• There are many hundreds of studies more not cited here confirming the therapeutic and prophylactic properties of these herbs.

♦ Footnotes:
  • [α] Comparative study of rosmarinic acid content in some plants of Labiatae family.
    Plants of Labiatae are used in traditional medicine and phytotherapy.
    Rosmarinic acid (RA) is a phenolic compound which is found in many genus of Labiatae and exhibits important biological activities.
    PMCID: PMC3307200 PMID: 22438661

  • [β] A Review of the Anti-Inflammatory Effects of Rosmarinic Acid on Inflammatory Diseases
    Inflammatory diseases are caused by abnormal immune responses and are characterized by an imbalance of inflammatory mediators and cells.
    In recent years, the anti-inflammatory activity of natural products has attracted wide attention. Rosmarinic acid (RosA) is a water-soluble phenolic compound that is an ester of caffeic acid and 3, 4-dihydroxyphenyl lactic acid.
    RosA has a wide range of pharmacological effects, including anti-oxidative, anti-apoptotic, anti-tumorigenic, and anti-inflammatory effects.
    The anti-inflammatory effects of RosA have been revealed through in vitro and in vivo studies of various inflammatory diseases like arthritis, colitis, and atopic dermatitis.
    This article mainly describes the preclinical research of RosA on inflammatory diseases and depicts a small amount of clinical research data.

    • Effect of Rosmarinic Acid on Inflammatory Diseases
    • Arthritis
    • Colitis
    • Atopic Dermatitis
    • Asthma
    • Allergic Rhinitis
    • Periodontal Diseases, Gum Disease
    • Acute Pancreatitis
    • Mastitis, Breast Inflammation
    Many reports have demonstrated that RosA has an important role in treating inflammatory diseases through multiple mechanisms, and RosA exerts anti-inflammatory effects to treat various diseases.
    Front. Pharmacol., 28 February 2020
♦ References
  • [1] Hepatoprotective activities of rosmarinic acid against extrahepatic cholestasis in rats.
    Results of cultured hepatic stellate cells further showed the impacts of rosmarinic acid which attenuated TGF-β1-induced stellate cell mitogenic and fibrogenic activation.
    Our findings support the concept that rosmarinic acid could serve as a hepatoprotective agent, and dietary rosmarinic acid supplementation may be beneficial in terms of improving cholestasis-related liver injury via mechanisms involving resolution of oxidative burden and down-regulation of HMGB1/TLR4, NF-κB, AP-1, and TGF-β1/Smad signaling.
    Food Chem Toxicol. 2017 Aug 5 ;108(Pt A):214-223. Epub 2017 Aug 5. PMID: 28789951

  • [2] Effect of p-cymene and rosmarinic acid on gastric ulcer healing - Involvement of multiple endogenous curative mechanisms.
    p-Cymene and rosmarinic acid are secondary metabolites found in several medicinal plants and spices.
    To evaluate their gastroduodenal antiulcer activity, gastric healing and toxicity in experimental models.
    In the HCl/ethanol-induced gastric ulcer and cysteamine-induced duodenal injury, p-cymene and rosmarinic acid (50-200 mg/kg) decreased significantly the ulcer area, and so prevented lesions formation.
    In the acetic acid-induced ulcer model, both compounds (200 mg/kg) markedly reduced the ulcerative injury.
    Data altogether suggest low toxicity, antiulcer and gastric healing activities of p-cymene and rosmarinic acid.
    Antioxidant and immunomodulatory properties seem to be involved in the curative effect as well as the induction of different factors linked to tissue repair.
    Phytomedicine. 2021 Feb 16:153497. Epub 2021 Feb 16. PMID: 33745762

  • [3] Effects of Rosmarinic Acid on Methotrexate-induced Nephrotoxicity and Hepatotoxicity in Wistar Rats. (known 'side effects of Methotrexate, highly toxic Chemotherapy agent used to treat Cancer)
    This study of rosmarinic acid (RA) is as an antioxidant on nephrotoxicity and hepatotoxicity induced by MTX.
    MTX significantly increased the urea, creatinine, ALT, AST, ALP levels, and renal MDA and significantly decreased renal catalase (CAT), hepatic glutathione (GSH), and hepatic CAT activity.
    RA (Rosmarinic Acid) at 100 mg/kg caused a significant decrease in ALT and AST and at two doses significantly decreased urea, renal MDA, and liver MDA.
    RA at 200 mg/kg significantly increased the renal CAT and liver GSH.
    RA in two doses significantly decreased necrosis and Leukocyte infiltration.
    RA caused a significant decrease in degeneration and cellular vacuolization in liver tissues.
    RA with its antioxidant and anti-inflammatory characteristics decreased the MTX induced nephrotoxicity and hepatotoxicity.
    Indian J Nephrol. 2021 May-Jun;31(3):218-224. Epub 2021 Jan 27. PMID: 34376933

  • [4] Ellagic acid and rosmarinic acid attenuate doxorubicin-induced testicular injury in rats.
    The anticancer drug doxorubicin causes testicular toxicity as an undesirable effect.
    Doxorubicin decreased testicular relative weight, sperm count, motility, serum testosterone, testicular glycogen, and sialic acid with increased incidence of histopathological changes, oxidative stress, tumor necrosis factor-alpha, as well as cholinesterase activity.
    Conversely, ellagic and rosmarinic acid treatment ameliorated such damage, thus showing the possibility to use as an adjuvant during doxorubicin treatment.
    J Biochem Mol Toxicol. 2017 Jun 6. Epub 2017 Jun 6. PMID: 28586512

  • [5] Prophylactic effects of ellagic acid and rosmarinic acid on doxorubicin-induced neurotoxicity in rats.
    Doxorubicin (DOX) is a chemotherapeutic agent widely used in human malignancies. Its long-term use cause neurobiological side effects.
    Our data showed that DOX-induced significant elevation of brain malondialdehyde, tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), caspase-3, and cholinesterase associated with significant reduction in reduced glutathione, monoamines namely serotonin, dopamine, as well as norepinephrine.
    Concomitant administration of EA (10 mg/kg/day, p.o. for 14 days) and/or RA (rosmarinic acid) (75 mg/kg/day, p.o.for 14 days) with DOX significantly mitigated the neural changes induced by DOX.
    Meanwhile, treatment ameliorated pro-inflammatory cytokines as TNF-α, iNOS, and attenuated oxidative stress biomarkers as well as brain monoamines.
    In conclusion, EA and RA can effectively protect against DOX-induced neurotoxicity, and the mechanisms underlying the neuroprotective effect are potentially associated with its antioxidant, anti-inflammatory, and antiapoptotic properties.
    J Biochem Mol Toxicol. 2017 Aug 16. Epub 2017 Aug 16. PMID: 28815802

  • [6] Effect of botanical extracts containing carnosic acid or rosmarinic acid on learning and memory in SAMP8 mice.
    Oxidative damage is one of the hallmarks of the aging process.
    The current study evaluated effects of two proprietary antioxidant-based ingredients, rosemary extract and spearmint extract containing carnosic acid and rosmarinic acid, respectively, on learning and memory in the SAMP8 mouse model of accelerated aging.
    Rosemary extract with 10% carnosic acid improved retention in T-maze foot shock avoidance and lever press.
    Spearmint with 5% rosmarinic acid improved acquisition and retention in T-maze foot shock avoidance and object recognition.
    4-hydroxynonenal (HNE) was reduced in the brain cortex after treatment with all three extracts (P<0.001) compared to the vehicle treated SAMP8.
    Protein carbonyls were reduced in the hippocampus after administration of rosemary with 10% carnosic acid (P<0.05) and spearmint containing 5% rosmarinic acid (P<0.001).
    The current results indicate that the extracts from spearmint and rosemary have beneficial effects on learning and memory and brain tissue markers of oxidation that occur with age in SAMP8 mice.
    Physiol Behav. 2016 Aug 12. Epub 2016 Aug 12. PMID: 27527000

  • [7] Doxorubicin (DOX) is an anticancer medicine that may trigger cardiomyopathy. Rosmarinic acid (RA) has shown antioxidant, anti-inflammatory, and anticancer effects.
    This investigation assessed the cardioprotective effect of RA on DOX-induced-toxicity in both in vivo and in vitro experiments.
    Administration of RA ameliorated the toxic effects of DOX.
    In vitro studies showed that RA did not affect the cytotoxic effect of DOX. (desired effect on cancer cells)
    RA as an antioxidant, anti-inflammatory, and cardioprotective compound could be a promising compound to help minimize DOX-induced cardiotoxicity.
    Nutr Cancer. 2021 Jun 4:1-15. Epub 2021 Jun 4. PMID: 34085575

  • [8] Lemon Balm and Its Constituent, Rosmarinic Acid, Alleviate Liver Damage in an Animal Model of Nonalcoholic Steatohepatitis.
    Nonalcoholic fatty liver disease (NAFLD) ranges in severity from hepatic steatosis to cirrhosis.
    Lemon balm and its major constituent, rosmarinic acid (RA), effectively improve the liver injury and obesity; however, their therapeutic effects on nonalcoholic steatohepatitis (NASH) are unknown.
    In this study, we investigated the effects of RA and a lemon balm extract (LBE) on NAFLD and liver fibrosis and elucidated their mechanisms.
    LBE and RA treatments alleviated the oxidative stress by increasing antioxidant enzymes and modulated lipid metabolism-related gene expression by the activation of adenosine monophosphate-activated protein kinase (AMPK) in vitro and in vivo.
    LBE and RA treatments inhibited the expression of genes involved in hepatic fibrosis and inflammation in vitro and in vivo.
    Together, LBE and RA could improve liver damage by non-alcoholic lipid accumulation and may be promising medications to treat NASH.
    Nutrients. 2020 Apr 22 ;12(4). Epub 2020 Apr 22. PMID: 32331258

  • [9] Perilla frutescens var. japonica and rosmarinic acid improve amyloid-β25-35 induced impairment of cognition and memory function.
    The accumulation of amyloid-β (Aβ) in the brain is a hallmark of Alzheimer's disease (AD) and plays a key role in cognitive dysfunction.
    Perilla frutescens var. japonica extract (PFE) and its major compound, rosmarinic acid (RA), have shown antioxidant and anti-inflammatory activities.
    Our present study demonstrated that PFE and RA administration significantly enhanced cognition function and object discrimination, which were impaired by Aβ25-35, in the T-maze and object recognition tests, respectively.
    In addition, oral administration of PFE and RA decreased the time to reach the platform and increased the number of crossings over the removed platform when compared with the Aβ25-35-induced control group in the Morris water maze test.
    Furthermore, PFE and RA significantly decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in the brain, kidney, and liver.
    In particular, PFE markedly attenuated oxidative stress by inhibiting production of NO and MDA in the Aβ25-35-injected mouse brain.
    These results suggest that PFE and its active compound RA have beneficial effects on cognitive improvement and may help prevent Alzheimer's Disease induced by Aβ.
    Nutr Res Pract. 2016 Jun ;10(3):274-81. Epub 2016 Apr 1. PMID: 27247723

  • [10] Prophylactic effect of rosmarinic acid on tracheal responsiveness, white blood cell count and oxidative stress markers in lung lavage of sensitized rats.
    Rosmarinic acid (RA) as an active component of several medicinal plants, has shown anti-inflammatory and anti-oxidant effects.
    In this study, the effect of RA on tracheal responsiveness (TR), lung inflammatory cells, oxidant biomarkers in sensitized rats were evaluated.
    The effect of RA medium concentration on percentage of eosinophils and RA high concentration on total WBC count and percentages of eosinophils and lymphocytes, were significantly higher than those of dexamethasone.
    These results showed the concentration-dependent effect of RA on tracheal responses, lung inflammatory cells and oxidant-antioxidant parameters which was comparable to that of dexamethasone at used concentrations in sensitized rats.
    Pharmacol Rep. 2018 Jan 17 ;70(1):119-125. Epub 2018 Jan 17. PMID: 29355815

  • [11] The Antioxidant Effect of Rosmarinic Acid by Different Delivery Routes in the Animal Model of Noise-Induced Hearing Loss.
    Trans-tympanic Rosmarinic Acid (RA), as compared with the systemic administration, protects against noise-induced auditory hair cell and hearing losses in rats in vivo.
    RA was administrated in male Wistar rats by trans-tympanic (20μl) and systemic (10 mg/kg) modality. In systemic administration, RA was injected 1 hour before noise exposure and once daily for the following 3 days.
    Systemic RA administration significantly decreased noise-induced hearing loss and the improvement of auditory function was paralleled by a significant reduction in cochlear oxidative stress.
    The effectiveness of Rosmarinic Acid given via trans-tympanic injection could be interesting for the future application of this minimally-invasive procedure in the treatment of ROS-induced hearing loss.
    Otol Neurotol. 2018 Mar ;39(3):378-386. PMID: 29424820

  • [12] Rosmarinic acid attenuates inflammation in experimentally induced arthritis in Wistar rats
    The experiment was conducted at doses of 25 and 50 mg/kg
    Rosmarinic acid significantly decreased the arthritic score, paw volume, joint diameter, white blood cell count and erythrocyte sedimentation rate.
    It also significantly increased body weight, hemoglobin and red blood cells.
    The significantly decreased levels of TNF-α were observed in treated groups as compared to arthritic control rats (P < 0.001).
    At the same time antioxidant parameters (like GSH and SOD) were increased significantly while levels of MDA were significantly decreased (P < 0.001).
    The outcome of the present research concludes that rosmarinic acid showed significant anti-arthritic potential in FCA-induced arthritis in Wistar rats.
    This study represented the therapeutic role of rosmarinic acid from Punica granatum for the management of arthritis/rheumatoid arthritis/osteoarthritis and related inflammatory complications with negligible side effects which was still far from complete mitigation with available conventional medicines.
    Int J Rheum Dis. 2019 Jun 2. Epub 2019 Jun 2. PMID: 31155849

  • [13] Evaluation of the virucidal effects of rosmarinic acid against enterovirus 71 infection via in vitro and in vivo study.
    Although enterovirus 71 (EV71) is an important public health threat, especially in the Asia-Pacific region, there are still no effective drugs or vaccines to treat and prevent EV71 infection.
    Therefore, it is critical to develop prophylactic and therapeutic agents against EV71. Rosmarinic acid (RA), a phytochemical, has been discovered to possess a broad spectrum of biological activities.
    RA showed a strong protective effect against EV71 infection in human rhabdomyosarcoma cells when the multiplicity of infection was 1, with a low IC value (4.33 ± 0.18 μM) and high therapeutic index (340).
    RA not only protected cells from EV71-induced cytopathic effects, but also from EV71-induced apoptosis.
    The results of time-of-addition analysis demonstrated that the inhibitory activity of RA was highest at the early stage of viral infection.
    This study suggests that RA has the potential to be developed as an antiviral agent against initial EV71 infection to prevent or reduce EV71-induced pathogenesis and complications, since RA can effectively reduce EV71 infection in the early stages of viral infection.
    Virol J. 2019 07 31 ;16(1):94. Epub 2019 Jul 31. PMID: 31366366

  • [14] Protective effect of RA on myocardial infarction (heart attack) induced-cardiac fibrosis via AT1R/p38 MAPK pathway signaling and modulation of the ACE2/ACE ratio.
    Rosmarinic acid (α-o-caffeoyl-3,4-dihydroxyphenyl lactic acid, RA), a major active constituent of Rosmarinus officinalis Linn. (rosemary), having significant anti-inflammatory, anti-apoptotic and anti-oxidant effects.
    Compared with the model group, RA treatment ameliorated the changes in left ventricular systolic pressure (LVSP), +dp/dtmax, and -dp/dtmax after 4 weeks.
    RA treatment was also associated with decreased angiotensin-converting enzyme (ACE) expression and increased ACE2 expression, as well as decreased expression of angiotensin type 1 receptor (AT1R) and phospho-p38 mitogen-activated protein kinase(p38 MAPK).
    Thus, RA can protect against cardiac dysfunction and fibrosis following MI, likely due to decreasing ACE expression and increasing ACE2 expression via AT1R/ p38 MAPK pathway.
    J Agric Food Chem. 2016 Aug 19. Epub 2016 Aug 19. PMID: 27538767

  • [15] Effect of rosmarinic acid on the arterial blood pressure in normotensive and hypertensive rats: Role of ACE.
    (1) rosmarinic acid caused systolic blood pressure dose-dependent decrease in hypertensive rats;
    (2) The angiotensin I dose-response curves demonstrated that rosmarinic acid promotes minor changes in systolic blood pressure only in the hypertensive group;
    The rosmarinic acid is effective in reducing blood pressure, selectively, only in hypertensive animals.
    The rosmarinic acid (173µM) promoted almost a 98.96% reduction on angiotensin-converting enzyme activity.
    Phytomedicine. 2018 Jan 1 ;38:158-165. Epub 2017 Feb 24. PMID: 29425648

  • [16] Rosmarinic acid inhibits proliferation and invasion of hepatocellular carcinoma cells SMMC 7721 via PI3K/AKT/mTOR signal pathway.
    To investigate the effect of rosmarinic acid (RosA) on hepatocellular carcinoma cell in vivo and in vitro and to explore its possible mechanism of anti-hepatocarcinoma.
    RosA significantly inhibited the proliferation of SMMC-7721 cells and induced G1 arrest and apoptosis in a dose-dependent manner.
    RosA might inhibit cell invasion by regulating epithelial-mesenchymal transition.
    RosA can inhibit the proliferation and invasion of hepatocellular carcinoma cell in vitro and inhibit tumour growth in vivo and the mechanism may relate to inhibiting the activation of PI3K/AKT signal pathway.
    Biomed Pharmacother. 2019 Sep 18 ;120:109443. Epub 2019 Sep 18. PMID: 31541884

  • [17] Rosmarinic Acid Attenuates Airway Inflammation and Hyperresponsiveness in a Murine Model of Asthma.
    Rosmarinic acid (RA) has numerous pharmacologic effects, including anti-oxidant, anti-inflammatory, and analgesic effects.
    The results demonstrated that RA markedly inhibited increases in inflammatory cells and Th2 cytokines in the bronchoalveolar lavage fluid (BALF), significantly reduced the total IgE and Ova-specific IgE concentrations, and greatly ameliorated airway hyperresponsiveness (AHR) compared with the control Ova-induced mice.
    Histological analyses showed that RA substantially decreased the number of inflammatory cells and mucus hypersecretion in the airway.
    These findings suggest that RA may effectively delay the progression of airway inflammation.
    Molecules. 2016 ;21(6). Epub 2016 Jun 13. PMID: 27304950

  • [18] Rosmarinic Acid Potently Detoxifies Amylin Amyloid and Ameliorates Diabetic Pathology in a Transgenic Rat Model of Type 2 Diabetes.
    Protein aggregation is associated with a large number of human protein-misfolding diseases, yet FDA-approved drugs are currently not available.
    Amylin amyloid and plaque depositions in the pancreas are hallmark features of type 2 diabetes.
    Moreover, these amyloid deposits are implicated in the pathogenesis of diabetic complications such as neurodegeneration.
    Rosmarinic Acid has significant efficacy in reducing human amylin oligomer levels in HIP rat sera as well as in sera from diabetic patients.
    Efficacy studies of RA treatment with the diabetic HIP rat model demonstrated significant reduction in amyloid islet deposition and strong mitigation of diabetic pathology.
    Our work provides new molecular mechanisms and efficacy insights for a model nutraceutical agent (or ‘bioceutical'; natural compound showing therapeutic or prophylactic efficacy) against type 2 diabetes and other aging-related protein-misfolding diseases.
    ACS Pharmacol Transl Sci. 2021 Aug 13 ;4(4):1322-1337. Epub 2021 Jul 21. PMID: 34423269

  • [19] Preventive effects of Salvia officinalis L. against learning and memory deficit induced by diabetes in rats: Possible hypoglycaemic and antioxidant mechanisms.
    Learning and memory impairment occurs in diabetes.
    Salvia officinalis L. (SO) has been used in Iranian traditional medicine as a remedy against diabetes.
    Diabetes induced deficits in acquisition and retrieval processes.
    SO (600 and 800mg/kg) and rosmarinic acid reversed learning and memory deficits induced by diabetes and improved cognition of healthy rats.
    SO prevented diabetes-induced acquisition and memory deficits through inhibiting hyperglycemia, lipid peroxidation as well as enhancing antioxidant defense systems. Therefore, SO and its principal constituent rosmarinic acid represent a potential therapeutic option against diabetic memory impairment which deserves consideration and further examination.
    Neurosci Lett. 2016 Apr 22 ;622:72-77. Epub 2016 Apr 22. PMID: 27113201

  • [20] Rosmarinic acid-induced apoptosis and cell cycle arrest in triple-negative breast cancer cells.
    Rosmarinic acid (RA) is a polyphenolic compound with various pharmacological properties, including, anti-inflammatory, immunomodulatory, and neuroprotective, as well as having antioxidant and anticancer activities.
    Results obtained show that RA significantly caused cytotoxic and antiproliferative effects in both cell lines in a dose- and time-dependent manner.
    Remarkably, RA induced cell cycle arrest-related apoptosis and altered the expression of many apoptosis-involved genes differently.
    In conclusion, the data suggest that the polyphenol Rosmarinic Acid may have a potential role in TNBC therapies, particularly in MDA-MB-468 cells.
    Eur J Pharmacol. 2020 Aug 1:173419. Epub 2020 Aug 1. PMID: 32750370

  • [21] Screening out the anti-insomnia components from Prunella vulgaris L. based on plasma pharmacochemistry combined with pharmacodynamic experiments and UPLC-MS/MS analysis.
    P. vulgaris have been reported to have anti-insomnia effects.
    This study clarified that mangiferin, rosmarinic acid and salviaflaside were considered as the anti-insomnia components of P. vulgaris.
    J Ethnopharmacol. 2021 Oct 28 ;279:114373. Epub 2021 Jun 26. PMID: 34181959
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