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Lovage

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Background & General Info

Lovage is a glabrous perennial plant that originates from Iran and Afghanistan but now has become globally widespread, especially in southern Europe, southwestern Asia, and Mediterranean region where it thrives in sunny mountain slopes and well-drained areas with moist fertile soil. [1] The entire plant and all its parts are strongly aromatic, with a distinctive earthy, celery-like smell and flavor. Lovage is widely cultivated for its seeds, leaves, and roots, which are universally used in the perfumery, food, beverage, and tobacco industries, either in their fresh or powdered forms or as essential oils. In several South European cuisines, lovage leaves and seeds are added to flavor the food and are incorporated in salads, broths, and broths, whereas the light yellow essential oils of lovage are used in aromatherapy with their distinctive sharp odor.

Scientifically referred to as Levisticum officinale, lovage belongs to the Apiaceae family, which comprises approximately 3,000 species. Interestingly, several of this family’s member species are commonly used in traditional medicine and possess scientifically verified medicinal properties attributable to the presence of bioactive secondary metabolites in all plant parts, such as essential oils, polyphenols, coumarins, saponins, alkaloids, and polyacetylenes, so it is not a surprise that lovage has a long history of medicinal use. [2]



Botany

Lovage is an erect, herbaceous plant that reaches a height of around 1.8–2.5 meters and whose stems and leaves smell very alike to celery when crushed. The plant possesses a short thick rootstock that produces a round, hollow, ribbed stem, which branches toward the top. Its glossy, dark green leaves are opposite and compound and decrease in size near the top; the broad triangular to rhomboidal, acutely pointed leaflets have a celery-like fragrance, with a few marginal teeth. The small, pale yellow to greenish-yellow flowers blossom from June to August and are arranged in compound globose umbels at the top of the stems. [3]

History & Traditional Use

The rich history of lovage as a medicinal plant and spice spans centuries, dating back to the days of ancient Romans. In most European regions, the use of lovage as a condimentary herb is frequent. Since the 4th century, the plant’s roots have been conventionally used for their carminative, spasmolytic, and diuretic effects and are usually incorporated as a component of herbal teas. The Trotula, a set of texts on women’s medicine written in the 12th century, recommended lovage for skin tightening. [1] It is noteworthy to mention that lovage is among the twelve most frequently used plants in the treatment of vesicle and kidney complaints. [4] German Commission E recommends the use of lovage in cases of lower urinary tract infections and urinary stones to increase urine flow. [5] In Iranian folk medicine, lovage is used as a cure for a spectrum of gastrointestinal, nervous, and rheumatic disorders. [6]

General Herbal Uses

Lovage ranks as one of the most valued herbs and plants with beneficial medicinal properties, especially its roots, fruits, and leaves, and this plant’s essential oil composition has been studied countless of times in different countries. The pharmaceutical industry is currently developing alcohol extract from this plant as treatment for kidney stones and urinary tract infections [7], and lovage is a source of traditional herbal medicinal products that can be used to deliberately boost urine volume to consequently flush the urinary tract in cases of mild urinary complaints. [8] Based on traditional medicinal systems, lovage enjoys strong diaphoretic, expectorant, stomachic, and stimulant activities. Lovage root, from which good amounts of volatile oil can be obtained, is medicinally important for the stimulation of digestion and for its antispasmodic, carminative, diuretic, and antiseptic effects. [9]

As an herbal tea or infusion for oral use, lovage can be consumed twice daily by adults and the elderly at a dose of 2–3 grams of comminuted herbal substance in 150 mL of boiling water. [8]



Constituents/Active Components

Lovage roots contain approximately 0.08 to 0.17% of the phthalide ligustilide, which partly contributes to the spasmolytic property of the plant. [4] An early 1990 study, using gas chromatography–mass spectrometry and gas chromatography–Fourier transform infrared spectroscopy, chemically examined the composition of the headspace lovage roots and identified 20 compounds, the principal ones being β-phellandrene (16.47%), citronellal (12.84%), and ligustilide (20.91%). [10]

As assessed by gas chromatography in the study of Sertel, Eichhorn, Plinkert, and Efferth (2011), the chemical composition of the lovage leaf essential oil is presented in the table below, which illustrates the main constituents in percentages (73.74 % of the total oil), of which monoterpenes are the major fraction. [11]

Lovage Compounds

Medicinal/Scientific Research

Antioxidant

Extracted through hydrodistillation, the essential oil of lovage had been observed to exert both anti-oxidant and antitumor activities. As assessed by DPPH method, the essential oil’s antioxidant activity was at an IC50 of 65 µg/mL, whereas its antitumor activity against HepG2 and MCF7 was 98% and 95%, respectively, at 100 µg/mL. However, at the same concentration, there was less activity observed against HT29, while at 50µg/mL, the essential oil displayed weak activity, with a 65% inhibition. With respect to the anti-inflammatory property of lovage, its petroleum ether and chloroform extracts that were provided at a dose of 200mg/kg body weight in rats showed anti-inflammatory action after 4 hours in carrageenan-induced edema models. [12]

Anticancer

Current treatment approaches to cancer involve an array of multiple therapy modalities, including surgery, radiation, and chemotherapy, but there has been a consistent search for alternative therapeutic strategy since advanced-stage cancers are likely associated with morbidity and poor patient outcomes. A number of studies have pointed to lovage as a valuable source of natural compounds and phytochemicals with anticancer activities. Plants of the Apiaceae family, to which lovage is a member of, contain a group of bioactive aliphatic C17-polyacetylenes that have cytotoxic effects against human cancer cells and have been found to reduce tumor formation in mammalian in vivo models. [2] In particular, extracts from lovage have been documented to possess antiproliferative and proapoptotic effects against a broad range of cancer cell lines. [9]

The essential oil derived from lovage leaves through steam distillation has been confirmed by Sertel, Eichhorn, Plinkert, and Efferth (2011) to inhibit the growth of head and neck squamous carcinoma cells in humans, exerting cytotoxic and antiproliferative activity against the aforementioned cancer cells. With an IC50 value of 292.6 ìg/mL, lovage leaf essential oil, in a dose–response curve, manifested a steady ascent in viability to 272.1% at 0.18 mg/mL, when compared to the untreated controls, and a succeeding swift decrease in viability to 4.7% at 0.54 mg/mL. Based on microarray hybridization, 678 genes were differentially expressed after lovage leaf essential oil treatment at an IC50 concentration of 292.6 ìg/mL and the genes associated with apoptosis, cancer, cellular growth and proliferation, and cell cycle regulation were the most notably affected. The extracellular signal-regulated kinase 5 (ERK5) signaling pathway, integrin-linked kinase (ILK) signaling pathway, and virus entry through endocytosis and p53 signaling were most significantly regulated as well. [11]

Apoptotic activities of ethanol extracts from lovage fruits have also been investigated by Bogucka-Kocka, Smolarz, and Kocki (2008) against cancer cell lines of human acute myeloblastic leukemia (ML-1), human acute T cell leukemia cells (J-45.01), human eosinophilic leukemia (EOL), human Caucasian promyelocytic leukemia (HL-60), human T cell leukemia lymphoblast (1301), human T cell leukemia (C-8166), human myeloma (U-266B1), human Caucasian normal B cell (WICL), and human T cell (H-9). [13]

Antibacterial

In the study of Schinkovitz, Stavri, Gibbons, and Bucar (2008), a significant antimycobacterial activity was displayed by a dichloromethane extract prepared from lovage roots against Mycobacterium fortuitum and Mycobacterium aurum in a microtiter plate dilution assay. Bioassay-guided fractionation as means of further analysis identified 3(R)-falcarinol (3(R)-(-)-1,9-heptadecadien-4,6-diin-3-ol] and 3(R)-8(S)-falcarindiol [3(R)-8(S)-(+)-1,9-heptadecadien-4,6-diin-3,8-diol] as the active constituents of the extract: the first compound has a minimum inhibitory concentration (MIC) of 16.4 ìM against M. fortuitum and M. aurum, whereas the second has MICs of 30.7 ìM and 61.4 ìM against M. fortuitum and M. aurum, respectively. As a point of reference, the antibiotic ethambutol exhibited MICs of 115.5 ìM and 3.4 ìM against the two Mycobacterium species tested, respectively, while isoniazid exerted an activity of 14.6 ìM against M. fortuitum and 29.2 ìM against M. aurum. [14] Among the 21 plants studied by Garvey, Rahman, Gibbons, and Piddock (2011) whose individual extracts were evaluated by bioassay for synergy with ciprofloxacin against Salmonella enterica serotype Typhimurium, the extract from lovage was considered the most active extract with efflux inhibitory activity against Gram-negative bacteria and showed the greatest synergy with five antibiotics. [15]

In view of their study findings confirming the antibacterial activities of ethanol and chloroform extracts of lovage, Ebrahimi et al. (2016) decisively recommended the possible use of lovage extracts in the control of bacterial infections caused by the examined pathogenic bacteria. The said extracts were produced by maceration method of lovage powder with 85% ethanol and chloroform after grinding. The results indicated that at a concentration of 3125 to 25000 ìg/mL, both extracts of lovage inhibited the growth of Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Salmonella enteritidis, all of which are multidrug-resistant Gram-negative bacteria with known resistance to various antimicrobial compounds. This study also verified the synergistic relationship between lovage extracts and ciprofloxacin, a well-known quinolone antibiotic, against all tested Gram-negative pathogenic bacteria. Efflux pumps in pathogenic bacteria appear to be involved in the expulsion of antimicrobial agents acting on the bacteria to the outer vicinity, which is one of several mechanisms that result in bacterial drug resistances. Regarding presumptive efflux activity, in S. enteritidis and E. coli, both lovage extracts increased the amount of ethidium bromide accumulation, implying reduced efflux, but this is not the case in P. aeruginosa and A. baumannii where only the ethanol extract exhibited synergy with ciprofloxacin and ethidium bromide accumulation. [16]

By means of disk diffusion method using Müller–Hinton agar, Mirjalili et al. (2010) also conducted their own assessment of the antibacterial activity of lovage essential oils against seven bacteria. In this study, lovage essential oil was acquired through hydrodistillation of air-dried samples of lovage at different developmental stages (flower, immature fruit, green mature fruit, and ripened fruit) and was examined at a concentration of 10 ìL per disk. Findings from the preliminary screening of lovage essential oil’s antibacterial activity demonstrated the oil’s potent inhibition of all tested bacteria, namely, Bacillus subtilis ATCC 9372, Enterococcus faecalis ATCC 15753, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, E. coli ATCC 25922, P. aeruginosa ATCC 27852, and Klebsiella pneumoniae ATCC 3583. High antibacterial activity was specifically observed against the tested Gram-positive bacteria, especially B. subtilis, and the Gram-negative bacterium E. coli, although lovage essential oil was only moderately active against K. pneumoniae and P. aeruginosa. The essential oils of mature and ripened fruits of lovage, having an MIC value of 0.90 mg/mL, displayed the highest activity against B. subtilis, whereas the essential oil from the mature fruit alone exhibited the highest activity against S. epidermidis. [6]

Neuroprotective

Owing to some studies demonstrating the anti-inflammatory and antioxidant effects of lovage, its extracts may have a noteworthy role to play in the restoration of nervous system injuries, which trigger the release of several inflammatory factors from the injured nerves’ fibers, resulting in morphological and biochemical changes in the injured point and, in spinal cord neurons, Wallerian degeneration of the cell bodies. Mahmoudzehi et al. (2016) screened the neuroprotective effectiveness of lovage ethanol extract on the sciatic nerves of injured experimental rats. The rats were randomly divided into five groups, two of which are the control and compression groups and three are the experimental groups treated with lovage ethanol extract at doses of 50, 75, and 100 mg/kg. In this study, the sciatic nerve was compressed for 60 seconds and lovage ethanol extract was intraperitoneally injected at the first, second, and third weeks of treatment. The overall results signified a considerably decreased density of α-motoneurons in the compression group as compared to the control group (p < 0.001) and a significantly increased density of α-motoneurons in all groups treated with 50,75, and 100 mg/kg of the ethanol extract as compared to the compression group (p < 0.01). Moreover, the experimental groups treated with the 100 mg/kg dose manifested the highest neuroprotective activity as compared to the compression group. [7]

Ligustilide, a known lipophilic constituent of lovage, has been reported to exert neuroprotective effects against permanent focal ischemia and transient forebrain ischemia and, in the study of Feng et al. (2012), to lessen brain damage while enhancing cognitive function in rat models of chronic cerebral hypoperfusion. In the study, chronic cerebral hypoperfusion was induced by permanent, bilateral occlusion of the common carotid artery in rats, which were then orally treated with 80 mg/kg of ligustilide for seven consecutive days starting from the eighth day after surgery. The treated rats displayed decreased escape latency and swimming distance from the third day in maze tests and increased percent time in the target quadrant following ligustilide intervention. Moreover, the study findings pointed out that neuronal loss, damage to dendrites, and neuronal apoptosis were effectively prevented by ligustilide in both the parietal cortex and hippocampus of rats. Ligustilide has also successfully hampered astrocytic activation and hypoperfusion-stimulated proliferation. [17]

Nephroprotective And Litolytic

A number of herbs, including lovage, have been validated by many studies to have a protective effect against urolithiatic renal cell damage due to their antioxidant and inhibitory activities against crystallization, and the herbaceous lovage has been traditionally used for kidney stones. A small study published in the Journal of Urology and Research in October 2016 explored the safety and therapeutic value of lovage in patients with cystinuria, a rare autosomal-recessive defect that causes stones made from cysteine to develop in the kidneys, ureters, and bladder. This recent study involved 18 patients who were instructed to orally consume one tablespoon of lovage extract twice a day for two weeks; 66.7% of all study participants have a positive history of familial cystinuria. Measurement before and after administration of L. officinale demonstrated a significant decrease in cysteine levels in the urine (164.3 ± 27.3 versus 108.9 ± 22 mg/dL; p = 0.02); a significantly reduced urine volume, from 1686.1 ± 204.1 mL to 1530.5 ± 180.9 mL (p = 0.03); and significant changes in urine creatinine values (1.18 ± 0.37 versus 1.09 ± 0.32 mg/dL; p = 0.09). A statistically significant negative correlation was also found between body mass index and the level of urine cystine (p = 0.04, r= −0.42). [18]

Contraindications, Interactions, And Safety

Lovage has been in herbal use for many centuries without special warning. The US Food and Drug Administration (FDA) considers lovage as generally safe for human consumption. However, well-designed animal or human clinical trials concerning its correct dose, safety, and tolerability are scant. [18] The EMA/HMPC does not advise the use and consumption of lovage tea and infusion in children and adolescents below 18 years old as a precaution and further suggests that the duration of their use should be limited to 2–4 weeks only. [8] Similar to any medicinal plant, if health concerns and symptoms such as fever, dysuria, spasm, or blood in urine persist or occur during lovage use, a professional healthcare practitioner or doctor should be consulted. Contraindications of lovage use include impaired kidney function or inflammation of the kidneys and hypersensitivity to the herb itself. Since no data exists about the safety of lovage during pregnancy and lactation, its use is best avoided.

References:

[1] A. Chevallier, Encyclopedia of Herbal Medicine, 3rd ed., New York: DK Publishing, 2016, p. 228. https://po717.files.wordpress.com/2017/01/b-e-s-t-1465449817-encyclopedia-herbal-medicine-andrew-chevallier.pdf

[2] L. Christensen and K. Brandt, "Bioactive polyacetylenes in food plants of the Apiaceae family: occurrence, bioactivity and analysis," Journal of Pharmaceutical and Biomedical Analysis, vol. 3, no. 683–693, p. 41, 2006. https://www.ncbi.nlm.nih.gov/pubmed/16520011

[3] P. Extension, "Herbs: Lovage," Penn State College of Agricultural Sciences, 2016. http://extension.psu.edu/plants/gardening/herbs/lovage

[4] S. Segebrecht and H. Schilcher, "Ligustilide: Guiding component for preparations of Levisticum officinale roots," Planta Medica, vol. 55, no. 6, p. 572–573, 1989. https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2006-962102

[5] M. Blumenthal, W. Busse and A. Goldberg, The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines, Austin, Texas: American Botanical Council, 1998. http://www.gbv.de/dms/bs/toc/302401350.pdf

[6] M. Mirjalili, P. Salehi, A. Sonboli, M. Yousefzadi, S. Ebrahimi and M. Yousefzadi, "The composition and antibacterial activity of the essential oil of Levisticum officinale Koch flowers and fruits at different developmental stages," Journal of the Serbian Chemical Society, vol. 75, no. 12, p. 1661–1669, 2010. https://www.researchgate.net/publication/49596408

[7] S. Mahmoudzehi, G. Dorrazehi, S. Jamalzehi, A. Khabbaz, F. Ghorbani, A. Hooti, A. Dadkani and M. Souran, "The neuroprotective effects of alcoholic extract of Levisticum officinale on alpha motoneurons’ degeneration after sciatic nerve compression in male rats," International Journal of Medical Research & Health Sciences, vol. 5, no. 9S, p. 647–653, 2016. http://textlab.io/doc/21858446/pdf-full-text

[8] EMA/HMPC/524621/2011, "Community herbal monograph on Levisticum officinale Koch, radix," European Medicines Agency, 27 March 2012. http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_- _Community_herbal_monograph/2012/05/WC500126835.pdf

[9] C. Danciu, S. Avram, P. Gaje, et al., "An evaluation of three nutraceutical species in the Apiaceae family from the Western part of Romania: antiproliferative and antiangiogenic potential," Journal of Agroalimentary Processes and Technologies, vol. 19, no. 2, p. 173–179, 2013. http://www.journal-of-agroalimentary.ro/admin/articole/83593L29_Vol_19_2__2013_173-179.pdf

[10] J.-Q. Cu, F. Pu, et al., "The chemical composition of lovage headspace and essential oils produced by solvent extraction with various solvents," Journal of Essential Oil Research, vol. 2, no. 2, 1990. https://www.researchgate.net/publication/254246009

[11] S. Sertel, T. Eichhorn, P. Plinkert and T. Efferth, "Chemical Composition and antiproliferative activity of essential oil from the leaves of a medicinal herb, Levisticum officinale, against UMSCC1 head and neck squamous carcinoma cells," Anticancer Research, vol. 31, no. 1, p. 185–191, 2011. https://www.ncbi.nlm.nih.gov/pubmed/21273597

[12] S. El-Hamid, Y. Abeer and S. Hendawy, "Anti-inflammatory, antioxidant, anti-tumor and physiological studies on Levisticum officinale-Koch plant," Planta Medica, vol. 75, p. PE62, 2009. https://www.researchgate.net/publication/240232398

[13] A. Bogucka-Kocka, H. Smolarz and J. Kocki, "Apoptotic activities of ethanol extracts from some Apiaceae on human leukaemia cell lines," Fitoterapia, vol. 79, no. 7–8, p. 487–497, 2008. https://www.ncbi.nlm.nih.gov/pubmed/18672039

[14] A. Schinkovitz, M. Stavri, S. Gibbons and F. Bucar, "Antimycobacterial polyacetylenes from Levisticum officinale," Phytotherapy Research, vol. 22, no. 5, p. 681–684, 2008. https://www.ncbi.nlm.nih.gov/pubmed/18350523

[15] M. Garvey, M. Rahman, S. Gibbons and L. Piddock, "Medicinal plant extracts with efflux inhibitory activity against Gram-negative bacteria," International Journal of Antimicrobial Agents, vol. 37, no. 2, p. 145–151, 2011. https://www.ncbi.nlm.nih.gov/pubmed/21194895

[16] A. Ebrahimi, A. Eshraghi, M. Mahzoonieh and S. Lotfalian, "Antibacterial and antibiotic-potentiation activities of Levisticum officinale L. extracts on pathogenic bacteria," International Journal of Infection, p. e38768, 2016. http://intjinfection.com/?page=article&article_id=38768

[17] Z. Feng, Y. Lu, X. Wu, P. Zhao, J. Li, et al., "Ligustilide alleviates brain damage and improves cognitive function in rats of chronic cerebral hypoperfusion," Journal of Ethnopharmacology, vol. 144, no. 2, p. 313–321, 2012. https://www.ncbi.nlm.nih.gov/pubmed/23022689

[18] M. Mohammadi, E. Parvaneh and Z. Tolou-Ghamari, "Clinical investigation of Levisticum officinale (lovage) effectiveness' in patients with cystinuria," Journal of Urology and Research, vol. 3, no. 6, p. 1071, 2016. https://www.jscimedcentral.com/Urology/urology-3-1071.pdf

Article researched and created by Dan Albir for herbs-info.com. © herbs-info.com 2018

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