- 1Centre of Environment Climate Change and Public Health, RUSA, Utkal University, Bhubaneswar, India
- 2Department of Biology, Animal Physiology and Neurobiology Section, KU Leuven, Leuven, Belgium
- 3Department of Pharmacy, School of Pharmacy and Medicine, College of Medicine and Health Sciences, University of Rwanda, Huye, Rwanda
- 4Graduate Program in Animal Science and Biotechnology Applied to Agriculture, Chemistry Laboratory of Natural Products, Paranaense University, Umuarama, Brazil
Editorial on the Research Topic
Ethnopharmacology of the lamiaceae: Opportunities and challenges for developing new medicines
The Lamiaceae (also known as the mint family) is one of the largest botanical families, with 6,900–7,200 accepted species names, under 236 genera. The importance of the family for medicinal, aromatic, environmental, and food purposes has been known for centuries. Species in the mint family are recognized in traditional medicine throughout the world. Some particularly prominent genera include Salvia (900 spp.), Scutellaria (360 spp.), Stachys (360 spp.), Hyptis (280 spp.), and Thymus (360 spp.). Many of the species are cultivated including several widely used culinary botanical drugs viz. Ocimum basilicum L.; Lavandula angustifolia Mill.; Origanum majorana L.; Mentha L.; Origanum vulgare L.; Rosmarinus officinalis L.; Salvia officinalis L.; Satureja hortensis L. and Thymus vulgaris L.
The focus of this research topic is to make a special contribution to the ethnopharmacology of the species that make up the Lamiaceae family; considering the phytochemistry and molecular pharmacology of its secondary metabolites. All the manuscripts that make up this edition show the importance of Lamiaceae and their secondary metabolites in the prevention and treatment of various diseases; evidencing that many drugs available today have their origin in plant molecules.
A very important topic in this issue assesses the influence of seasonality on the chemical composition and biological activities of species that make up the Mentha genus, common to the Mediterranean and subtropical regions, and has received considerable attention for being a rich source of a variety of phenolic compounds and also for its numerous therapeutic properties (Abbou et al., 2022). However, the variability and alteration of phytochemical composition due to different ecological and geographical factors can lead to differences in biological activities and pharmaceutical properties of the plant (Mollaei et al., 2020). Brahmi et al. studied the influence of environmental factors on the levels of phenolic compounds of three species of the genus Mentha (M. pulegium, M. rotundifolia, and M. spicata) from different regions of Algeria. The authors, based on phytochemical analyses, conclude that the phenolic content observed highest in distinct regions, probably due to environmental factors such as soil nature, altitude, temperature, and precipitations, conjugated with eventual region-dependent biotic factors. Also, variation in antioxidant capacity was observed according to geographical and ecological factors. The results obtained in this study allowed determining the best local conditions for the growth of the studied species for a higher concentration of phenolic compounds and their possible use in different fields such as health care and food. Nevertheless, more research is needed to precise the causes of location effects, extend the study over several years, determine the heritability of phenolic compounds and antioxidant properties, and develop a production system that ensures exploitable biomasses.
Menthol (the key monoterpene found in Mentha × piperita L.) is known to modulate the nociceptive threshold and is present in different curative preparations that reduce sensory hypersensitivities in pain conditions. Pulegone is another similar type of compound present in Calamintha nepeta used in traditional medicine to alleviate rheumatic disorders, a chronic inflammatory disease. With advancements in gas chromatography-mass spectrometry, Hilfiger et al. studied in vitro anti-inflammatory activities of menthol and pulegone by measuring the secretion of the tumor necrosis factor-alpha (TNF α) from LPS-stimulated THP-1 cells. Furthermore, both menthol and pulegone have been tested for in vivo anti-hyperalgesic effects with a rat inflammatory pain model. In vivo rat model study showed pulegone to exert a higher transient anti-hyperalgesic effect on the nociceptive sensory thresholds than menthol; the authors compared the impacts of menthol and pulegone on inflammation and pain. Interestingly, both compounds act as strong anti-inflammatory and anti-hyperalgesic monoterpenes. Authors claimed that pulegone and menthol are the most abundant monoterpenes found in C. nepeta (49.41%) and M. piperita (42.85%) extracts, respectively. This is the first report of pulegone as anti-hyperalgesic suggesting that traditional treatments based on C. nepeta and M. piperita preparations have indeed the potential to reduce pain and inflammation. Further studies comparing the toxicity of pulegone and menthol at the therapeutic dose and their in-depth mechanisms of action will be required to assess their potential as drug candidates.
In a very elegant study, Berdowska et al. assessed the modulatory impact of Lamiaceae phytoconstituents on the apoptosis of human leukemia cells. The authors evaluated the impact of some dried aqueous extracts (Thymus vulgaris L., Thymus serpyllum L., Origanum majorana L., and Mentha × piperita L.) along with known phenolic compounds (caffeic acid, rosmarinic acid, lithospermic acid, luteolin-7-O-β-glucuronide, luteolin-7-O-rutinoside, eriodictyol-7-O-rutinoside, and arbutin) on both unstimulated and staurosporine-stimulated Jurkat cells. The results suggested the pro-apoptotic actions against human leukemia Jurkat cells of polyphenolic mixtures derived from T. serpyllum and O. majorana, enhancement of staurosporine-induced apoptosis by both caffeic and rosmarinic acids, and less evident pro-apoptotic effects of purified (poly)phenolic compounds. Nevertheless, due to the limitation of the present study, if longer incubation time and greater concentrations of the tested compounds had been applied, stronger effects might have been observed. Therefore, the present experiments may be considered rather as a pilot study to encourage their continuation with the aim to gain more definite conclusions.
Salvia is another significant genus of the Lamiaceae that is used worldwide for its medicinal and culinary uses. Most of the ethnopharmacological and phytochemical studies on Salvia are focused on species from the Asian and European clades. Hence, studies on the Neotropical sages (Salvia subgenus Calosphace; 587 spp.), are comparatively sporadic. Ortiz-Mendoza et al. compiled on the traditional uses, pharmacological and phytochemistry properties of the Mexican Neotropical Sages. The most common occurrences of active compounds are composed of the diterpenes, particularly clerodanes (e.g., Amarisolide A, Tilifodiolide). Research on these metabolites guided by the phylogenies is recommended since closely related species tend to share the presence of similar compounds and thus similar medicinal properties.
Selected members of the Lamiaceae family are widely used in traditional medicine to cure various disorders with some as potent cardioprotective plants (Patrignani et al., 2021). One of the best examples of a plant currently being used in developing a new hypertension drug is Marrubium vulgare L. The crude oil of M. vulgare was examined for hypotensive effect, which was scientifically proven due to the presence of diterpenoids (Michel et al., 2020).
And in this sense, Chakrabartty et al. performed an extensive literature review of members of Lamiaceae with antioxidant, anti-hyperlipidemic, vasorelaxant, and thrombolytic effects. The authors described different contributions of plants to different aspects of cardiovascular diseases like stroke, heart attack, etc. evidencing those phenolic acids, flavonoids, alkaloids, and other phytochemicals are responsible for these actions. Another point addressed in this research is functional foods, revealing that these plants are a rich source of nutrients and minerals such as omega-3, which may have an additional role in the prevention of cardiovascular diseases. Furthermore, the authors conclude that limitations still exist and that extensive research needs to be carried out on the Lamiaceae family in the quest to develop new and effective botanical drugs as well as functional foods that can be used in the treatment and prevention of diseases. cardiovascular diseases worldwide.
The rapid rising of antimicrobial resistance and the need for new approaches to fill the gap in antimicrobial drug discovery are alarming (Jouneghani et al., 2020). Tetradenia riparia Hochsteter codd. A plant belonging to Lamiaceae is being used to treat several bacterial and fungal infections. This species has been researched for decades to isolate and identify several chemical constituents such as ibozol, 7α-hydroxyroileanone, 1′,2′-dideacetylboronolide, 8 (14),15-sandaracopimaradiene-7α,18-diol; 5,6-dihydro-α-pyrone and α-pyrone. The compound 8 (14),15- sandaracopimaradiene-7α, 18-diol has demonstrated multiple bioactivities, such as antispasmodic, anthelmintic, and antimicrobial (foodborne pathogens, MDR Staphylococcus and Mycobacterium). Biofilm-producing bacteria are typically much less sensitive to antimicrobials than planktonic cells (Sahoo et al., 2021). Interestingly, the extract of T. riparia had strong effects against pre-formed S. aureus biofilm with clear disruption of organized structure of S. aureus ATCC 29213 biofilms under SEM (Endo et al., 2018). Moreover, Costa et al. (2015) found that a hydroalcoholic extract of T. riparia inhibited C. albicans biofilm which was more effective compared with standard fluconazole. Extract as well as the compound 8 (14),15-sandaracopimaradiene-7α,18-diol were found to be bactericidal against S. aureus, with antibiofilm activity (BIC50, 8.8 ± 1.5 μg/ml) (Van Puyvelde et al., 2021). Moreover, Endo et al. (2018) combined the hydroalcoholic extract along with penicillin against a panel of MDR S. aureus strains and found synergistic effects. A similar observation was also observed by Costa et al. (2015) when combined with nystatin against C. albicans. Other major bioactive compounds are 6,7-dehydroroyleanone (antimicrobial, antiparasitic), ibozol (antimicrobial, antitumor), and abieta-7,9 (11)-dien-13-β-ol (antimicrobial) was also testified from several experimental investigations.
The present research topic thus includes interdisciplinary research work expanding the knowledge about traditional uses of Lamiaceae fostering the scientific field of ethnopharmacology globally. This research topic successfully gathered comprehensive information in the field of drug discovery related to hyperalgesia, cardiovascular diseases, and cancer. Additional work is needed to isolate and characterize the active compounds and further follow–up studies are also necessary to elucidate the mechanism of action and SAR. Moreover, pharmacokinetic and toxicity studies will be required to assess their potential as drug candidates.
In view of what has been exposed in this special issue, we understand that despite the discovery of many compounds with high biological potential, further studies are needed to assess their toxicity as well as clinical studies. The limitation of this special issue is that the published papers are mostly focused on ethnopharmacology (regional, traditional, or cross-cultural practices), qualitative and quantitative composition of secondary metabolites, and identification of bioactive compounds (GC-MS, LC-MS, NMR) but lack studies on the development of molecular targets for drug discovery, randomized controlled clinical trials on the efficacy and safety of any Lamiaceae plants, either alone or in combination with western medicine. Moreover, most of the original research focuses on essential oil while follow-up with bioassay-guided purification is lacking, which needs to be followed up specially from the genera that are insufficiently explored. Many of the members of the Lamiaceae family often become matters for scientific validation but are not yet much explored, and scientists must give attention to their study in the near future.
We would like to thank all the reviewers for their comments that improved our manuscripts, and the authors for their excellent contributions.
We hope that this article collection will inspire scientists from different fields of research focusing on the assessment of traditional medicine, derived from Lamiaceae or other plant families, in the search for new pharmacological strategies.
Author contributions
All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.
Acknowledgments
The author SKP is thankful to the RUSA 2.0 for supporting the Centre of Excellence in Environment, Climate Change and Public Health (ECCPH), Utkal University. ZCG is thankful to Universidade Paranaense, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Araucária for the financial support and the fellowship. LVP and MJM largely funded themselves.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
Abbou, F., Azzi, R., Ouffai, K., El Haci, I. A., Belyagoubi-Benhammou, N., Bensouici, C., et al. (2022). Phenolic profile, antioxidant and enzyme inhibitory properties of phenolic-rich fractions from the aerial parts of Mentha pulegium L. S. Afr. J. Bot. 146, 196–204. doi:10.1016/j.sajb.2021.10.024
Costa, G. M., Endo, E. H., Cortez, D. A. G., Ueda-Nakamura, T., Nakamura, C. V, and Prado Dias Filho, B. P. D. (2015). Effect of plant extracts on planktonic growth and biofilm of Staphylococcus aureus and. Candida albicans. Int. J. Curr. Microbiol. App. Sci. 4 (6), 908–917.
Endo, E. H., Costa, G. M., Makimori, R. Y., Ueda-Nakamura, T., Nakamura, C. V., and Dias Filho, B. P. (2018). Anti-biofilm activity of Rosmarinus officinalis, Punica granatum and Tetradenia riparia against methicillin-resistant Staphylococcus aureus (MRSA) and synergic interaction with penicillin. J. Herb. Med. 14, 48–54. doi:10.1016/j.hermed.2018.07.001
Jouneghani, R. S., Castro, A. H. F., Panda, S. K., Swennen, R., and Luyten, W. (2020). Antimicrobial activity of selected banana cultivars against important human pathogens, including candida biofilm. Foods 9, E435. doi:10.3390/foods9040435
Michel, J., Abd Rani, N. Z., and Husain, K. (2020). A review on the potential use of medicinal plants from Asteraceae and Lamiaceae plant family in cardiovascular diseases. Front. Pharmacol. 11, 852–926. doi:10.3389/fphar.2020.00852
Mollaei, S., Ebadi, M., Hazrati, S., Habibi, B., Gholami, F., and Sourestani, M. M. (2020). Essential oil variation and antioxidant capacity of mentha pulegium populations and their relation to ecological factors. Biochem. Syst. Ecol. 91, 104084. doi:10.1016/j.bse.2020.104084
Patrignani, F., Prasad, S., Novakovic, M., Marin, P. D., and Bukvicki, D. (2021). Lamiaceae in the treatment of cardiovascular diseases. Front. Biosci. 26 (4), 612–643. doi:10.2741/4909
Sahoo, A., Swain, S. S., Behera, A., Sahoo, G., Mahapatra, P. K., and Panda, S. K. (2021). Antimicrobial peptides derived from insects offer a novel therapeutic option to combat biofilm: A review. Front. Microbiol. 12, 661195. doi:10.3389/FMICB.2021.661195
Van Puyvelde, L., Aissa, A., Panda, S. K., De Borggraeve, W. M., Mukazayire, M. J., and Luyten, W. (2021). Bioassay-guided isolation of antibacterial compounds from the leaves of Tetradenia riparia with potential bactericidal effects on food-borne pathogens. J. Ethnopharmacol. 273, 113956. doi:10.1016/J.JEP.2021.113956
Keywords: lamiaceae, drug discovery, phytochemistry, cardio vascular diseases, antiapoptosis, anti-hyperalgesic, antioxidant
Citation: Panda SK, Van Puyvelde L, Mukazayire MJ and Gazim ZC (2022) Editorial: Ethnopharmacology of the lamiaceae: Opportunities and challenges for developing new medicines. Front. Pharmacol. 13:961486. doi: 10.3389/fphar.2022.961486
Received: 04 June 2022; Accepted: 30 June 2022;
Published: 25 August 2022.
Edited and reviewed by:
Michael Heinrich, University College London, United KingdomCopyright © 2022 Panda, Van Puyvelde, Mukazayire and Gazim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Sujogya Kumar Panda, c3Vqb2d5YXBhbmRhQHV0a2FsdW5pdmVyc2l0eS5hYy5pbg==