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Used as a spice in various, particularly Mediterranean, cuisines and in traditional medicine for hundreds of years, this aromatic shrub has been the focus of substantial research this century to clarify its roles in skin care. It is used broadly in cosmetic formulations, particularly to preserve the product, and acts as a skin conditioner and fragrance in safe concentrations.1 Rosemary essential oil is also a popular choice frequently used in aromatherapy.2,3 This column focuses on recent promising results supporting the antioxidant and anti-photoaging activities, especially, of rosemary.
UV Protection and Rosemary in Combination
A 2021 study in mice authored by Auh and Madhavan showed that a mixture of marigold and rosemary extracts yielded anti-photoaging effects, with the botanical formula suppressing UV-induced damage.4
Seven years earlier, Pérez-Sánchez et al. combined rosemary and citrus extracts and found that they exerted protective effects against UV damage in human HaCaT keratinocytes as well as human volunteers after oral consumption. Significant increases in minimal erythema dose (MED) were seen in participants, with daily intake of 250 mg of botanical combination, at 8 weeks (34%) and 12 weeks (56%). The investigators attributed the photoprotective effects of the formula to rosemary polyphenols and diterpenes as well as citrus flavonoids.5
Evaluation of a human skin cell model by Sánchez-Marzo et al. in 2020 revealed that rosemary diterpenes were instrumental in an herbal extract that combined citrus, olive, and rosemary in conferring genoprotection against UV-induced DNA damage. The authors note that human trials are needed to overcome the limitations of the cellular model in ascertaining whether the tested herbal formulations can yield oral and/or topical photoprotection.6
Anti-Photoaging and Anti-Pollution
In 2022, Ibrahim et al. assessed a hexane extract of rosemary leaves for anti-photoaging activity. Their evaluation showed an abundance of triterpenoids, monoterpenoids, and phenolic diterpenes in rosemary, with in vitro assays verifying the anti-aging, antioxidant, and wound healing functions of the extract. Further, topical rosemary hexane extract–loaded lipid nanocapsules protected rat skin from UV radiation, as epidermal and dermal histological parameters improved, antioxidant biochemical balance was restored, and inflammatory markers and wrinkling were diminished. The researchers concluded that the use of rosemary hexane extract represents a safe, efficient, and cost-effective way to deliver anti-aging, photoprotective functions to cosmeceutical formulations.7
In March 2021, Nobile et al. published a report on their randomized, double-blind, placebo-controlled parallel group study to investigate the efficacy of a marketed polyphenol-enriched dietary supplement (Zeropollution, which contains four standardized herbal extracts: Olea europaea leaf, Lippia citriodora, S. rosmarinus, and Sophora japonica) in diminishing pollution-induced oxidative stress and in improving skin aging in 100 White and Asian women who were outdoor workers living in a polluted environment (Milan, Italy). Statistically significant improvements in reducing wrinkle depth and hyperpigmentation, enhancing elasticity and firmness, as well as promoting skin moisturization and diminishing transepidermal water loss were noted as early as 2 weeks after product consumption began, with inter-group and intra-group analysis verifying that all skin parameters were ameliorated in Asian and White subjects.8
Previously, Nobile et al. conducted a randomized, parallel-group study on 90 subjects to evaluate the photoprotective effects of a combination of rosemary and grapefruit (Citrus paradisi) extracts (Nutroxsun). The investigators also performed a pilot, randomized crossover study on five participants. Both studies included only females with Fitzpatrick skin phototypes I-III who manifested mild to moderate chronological aging or photoaging. Within as little as 2 weeks, treated individuals exhibited reductions in UVA- and UVB-induced skin changes. Skin elasticity improved in this group, with wrinkles diminishing along with skin redness and lipoperoxides. The investigators concluded that the oral blend of rosemary and grapefruit consumed long term merits consideration as an adjuvant approach to preventing the deleterious effects of solar exposure.9
In 2021, Hoskin et al. used ex vivo human biopsies exposed to diesel engine exhaust to study the impact of spray-dried algae-rosemary particles against pollution-induced damage. The spirulina-rosemary gel that was developed lowered levels of 4-hydroxynonenal protein adducts (4HNE-PA) as well as matrix metalloproteinase-9 (MMP-9) and reduced the loss of filaggrin. The researchers concluded that their topically applied spirulina-rosemary gel was effective in mitigating or preventing skin aging and cutaneous damage caused by diesel air pollution.10
Antioxidant, Antibacterial, and Anti-Inflammatory Activity
Based on a 2023 literature search by Li Pomi et al. of in vitro as well as in vivo animal and human studies involving S. rosmarinus and the skin, researchers reported on substantial evidence buttressing the antioxidant role of the botanical agent. They cautioned that, while data support the harnessing of the bioactive constituents of rosemary to address inflammatory and infectious skin conditions, large controlled trials remain necessary to establish its potential functions in dermatologic clinical practice.11
Ten years earlier, Park et al. determined that a phenolic diterpene from rosemary (carnosic acid) prevented UV-induced expression of MMP-1, MMP-3, and MMP-9 in human skin fibroblasts and keratinocytes in a concentration-dependent manner by suppressing reactive oxygen species and blocking through the inhibition of ROS and the suppression of extracellular signal-regulated kinase (ERK)-mediated AP-1 activation.12
Around the same time, Sienkiewicz et al. showed that rosemary essential oil exhibits antibacterial activity against the standard strain Escherichia coli ATCC 25922 and 60 other clinical strains of the bacteria.13
Further, anti-inflammatory properties have been attributed to rosemary essential oil, which are thought to be due to its suppression of nuclear factor kappa B transcription and inhibition of the arachidonic acid cascade.14
Other Functions of Rosemary
In 2022, Sutkowska-Skolimowska et al. demonstrated that rosemary extract in concentrations of 50 and 100mcg/mL significantly diminished accumulated collagen in the fibroblasts of four patients with severe and fatal osteogenesis imperfecta, suggesting that the botanical agent may have a role targeting cellular stress and inducing autophagy in therapy for this condition.15
In 2015, Akbari et al. established that 0.5% and 1% concentrations of rosemary essential oil were effective in facilitating the percutaneous absorption of diclofenac sodium topical gel.16
Conclusion
In Western culture, rosemary is thought of more as a spice to add flavor to food. However, there appears to be an emerging body of evidence suggesting various possible functions for rosemary in the dermatologic armamentarium. Much more research is necessary, though, to ascertain the most appropriate and optimal roles for this popular herb in skin care.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami, Florida. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a SaaS company used to generate skin care routines in office and as a ecommerce solution. Write to her at dermnews@mdedge.com.
References
1. González-Minero FJ et al. Cosmetics. 2020 Oct 3;7(4):77.
2. Sayorwan W et al. Sci Pharm. 2013 Apr-Jun;81(2):531-42.
3. Pazyar N et al. Skin Pharmacol Physiol. 2014;27(6):303-10.
4. Auh JH and Madhavan J Biomed Pharmacother. 2021 Mar;135:111178.
5. Pérez-Sánchez A et al. J Photochem Photobiol B. 2014 Jul 5;136:12-8.
6. Sánchez-Marzo N et al. Antioxidants (Basel). 2020 Mar 20;9(3):255.
7. Ibrahim N et al. Sci Rep. 2022 Jul 30;12(1):13102.
8. Nobile V et al. Food Nutr Res. 2021 Mar 29:65.
9. Nobile V et al. Food Nutr Res. 2016 Jul 1;60:31871.
10. Hoskin R et al. Molecules. 2021 Jun 22;26(13):3781.
11. Li Pomi F et al. Antioxidants (Basel). 2023 Mar 9;12(3):680.
12. Park M et al. Exp Dermatol. 2013 May;22(5):336-41.
13. Sienkiewicz M et al. Molecules. 2013 Aug 5;18(8):9334-51.
14. Borges RS et al. J Ethnopharmacol. 2019 Jan 30;229:29-45.
15. Sutkowska-Skolimowska. Int J Mol Sci. 2022 Sep 7;23(18):10341.
16. Akbari J et al. Pharm Biol. 2015;53(10):1442-7.
Used as a spice in various, particularly Mediterranean, cuisines and in traditional medicine for hundreds of years, this aromatic shrub has been the focus of substantial research this century to clarify its roles in skin care. It is used broadly in cosmetic formulations, particularly to preserve the product, and acts as a skin conditioner and fragrance in safe concentrations.1 Rosemary essential oil is also a popular choice frequently used in aromatherapy.2,3 This column focuses on recent promising results supporting the antioxidant and anti-photoaging activities, especially, of rosemary.
UV Protection and Rosemary in Combination
A 2021 study in mice authored by Auh and Madhavan showed that a mixture of marigold and rosemary extracts yielded anti-photoaging effects, with the botanical formula suppressing UV-induced damage.4
Seven years earlier, Pérez-Sánchez et al. combined rosemary and citrus extracts and found that they exerted protective effects against UV damage in human HaCaT keratinocytes as well as human volunteers after oral consumption. Significant increases in minimal erythema dose (MED) were seen in participants, with daily intake of 250 mg of botanical combination, at 8 weeks (34%) and 12 weeks (56%). The investigators attributed the photoprotective effects of the formula to rosemary polyphenols and diterpenes as well as citrus flavonoids.5
Evaluation of a human skin cell model by Sánchez-Marzo et al. in 2020 revealed that rosemary diterpenes were instrumental in an herbal extract that combined citrus, olive, and rosemary in conferring genoprotection against UV-induced DNA damage. The authors note that human trials are needed to overcome the limitations of the cellular model in ascertaining whether the tested herbal formulations can yield oral and/or topical photoprotection.6
Anti-Photoaging and Anti-Pollution
In 2022, Ibrahim et al. assessed a hexane extract of rosemary leaves for anti-photoaging activity. Their evaluation showed an abundance of triterpenoids, monoterpenoids, and phenolic diterpenes in rosemary, with in vitro assays verifying the anti-aging, antioxidant, and wound healing functions of the extract. Further, topical rosemary hexane extract–loaded lipid nanocapsules protected rat skin from UV radiation, as epidermal and dermal histological parameters improved, antioxidant biochemical balance was restored, and inflammatory markers and wrinkling were diminished. The researchers concluded that the use of rosemary hexane extract represents a safe, efficient, and cost-effective way to deliver anti-aging, photoprotective functions to cosmeceutical formulations.7
In March 2021, Nobile et al. published a report on their randomized, double-blind, placebo-controlled parallel group study to investigate the efficacy of a marketed polyphenol-enriched dietary supplement (Zeropollution, which contains four standardized herbal extracts: Olea europaea leaf, Lippia citriodora, S. rosmarinus, and Sophora japonica) in diminishing pollution-induced oxidative stress and in improving skin aging in 100 White and Asian women who were outdoor workers living in a polluted environment (Milan, Italy). Statistically significant improvements in reducing wrinkle depth and hyperpigmentation, enhancing elasticity and firmness, as well as promoting skin moisturization and diminishing transepidermal water loss were noted as early as 2 weeks after product consumption began, with inter-group and intra-group analysis verifying that all skin parameters were ameliorated in Asian and White subjects.8
Previously, Nobile et al. conducted a randomized, parallel-group study on 90 subjects to evaluate the photoprotective effects of a combination of rosemary and grapefruit (Citrus paradisi) extracts (Nutroxsun). The investigators also performed a pilot, randomized crossover study on five participants. Both studies included only females with Fitzpatrick skin phototypes I-III who manifested mild to moderate chronological aging or photoaging. Within as little as 2 weeks, treated individuals exhibited reductions in UVA- and UVB-induced skin changes. Skin elasticity improved in this group, with wrinkles diminishing along with skin redness and lipoperoxides. The investigators concluded that the oral blend of rosemary and grapefruit consumed long term merits consideration as an adjuvant approach to preventing the deleterious effects of solar exposure.9
In 2021, Hoskin et al. used ex vivo human biopsies exposed to diesel engine exhaust to study the impact of spray-dried algae-rosemary particles against pollution-induced damage. The spirulina-rosemary gel that was developed lowered levels of 4-hydroxynonenal protein adducts (4HNE-PA) as well as matrix metalloproteinase-9 (MMP-9) and reduced the loss of filaggrin. The researchers concluded that their topically applied spirulina-rosemary gel was effective in mitigating or preventing skin aging and cutaneous damage caused by diesel air pollution.10
Antioxidant, Antibacterial, and Anti-Inflammatory Activity
Based on a 2023 literature search by Li Pomi et al. of in vitro as well as in vivo animal and human studies involving S. rosmarinus and the skin, researchers reported on substantial evidence buttressing the antioxidant role of the botanical agent. They cautioned that, while data support the harnessing of the bioactive constituents of rosemary to address inflammatory and infectious skin conditions, large controlled trials remain necessary to establish its potential functions in dermatologic clinical practice.11
Ten years earlier, Park et al. determined that a phenolic diterpene from rosemary (carnosic acid) prevented UV-induced expression of MMP-1, MMP-3, and MMP-9 in human skin fibroblasts and keratinocytes in a concentration-dependent manner by suppressing reactive oxygen species and blocking through the inhibition of ROS and the suppression of extracellular signal-regulated kinase (ERK)-mediated AP-1 activation.12
Around the same time, Sienkiewicz et al. showed that rosemary essential oil exhibits antibacterial activity against the standard strain Escherichia coli ATCC 25922 and 60 other clinical strains of the bacteria.13
Further, anti-inflammatory properties have been attributed to rosemary essential oil, which are thought to be due to its suppression of nuclear factor kappa B transcription and inhibition of the arachidonic acid cascade.14
Other Functions of Rosemary
In 2022, Sutkowska-Skolimowska et al. demonstrated that rosemary extract in concentrations of 50 and 100mcg/mL significantly diminished accumulated collagen in the fibroblasts of four patients with severe and fatal osteogenesis imperfecta, suggesting that the botanical agent may have a role targeting cellular stress and inducing autophagy in therapy for this condition.15
In 2015, Akbari et al. established that 0.5% and 1% concentrations of rosemary essential oil were effective in facilitating the percutaneous absorption of diclofenac sodium topical gel.16
Conclusion
In Western culture, rosemary is thought of more as a spice to add flavor to food. However, there appears to be an emerging body of evidence suggesting various possible functions for rosemary in the dermatologic armamentarium. Much more research is necessary, though, to ascertain the most appropriate and optimal roles for this popular herb in skin care.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami, Florida. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a SaaS company used to generate skin care routines in office and as a ecommerce solution. Write to her at dermnews@mdedge.com.
References
1. González-Minero FJ et al. Cosmetics. 2020 Oct 3;7(4):77.
2. Sayorwan W et al. Sci Pharm. 2013 Apr-Jun;81(2):531-42.
3. Pazyar N et al. Skin Pharmacol Physiol. 2014;27(6):303-10.
4. Auh JH and Madhavan J Biomed Pharmacother. 2021 Mar;135:111178.
5. Pérez-Sánchez A et al. J Photochem Photobiol B. 2014 Jul 5;136:12-8.
6. Sánchez-Marzo N et al. Antioxidants (Basel). 2020 Mar 20;9(3):255.
7. Ibrahim N et al. Sci Rep. 2022 Jul 30;12(1):13102.
8. Nobile V et al. Food Nutr Res. 2021 Mar 29:65.
9. Nobile V et al. Food Nutr Res. 2016 Jul 1;60:31871.
10. Hoskin R et al. Molecules. 2021 Jun 22;26(13):3781.
11. Li Pomi F et al. Antioxidants (Basel). 2023 Mar 9;12(3):680.
12. Park M et al. Exp Dermatol. 2013 May;22(5):336-41.
13. Sienkiewicz M et al. Molecules. 2013 Aug 5;18(8):9334-51.
14. Borges RS et al. J Ethnopharmacol. 2019 Jan 30;229:29-45.
15. Sutkowska-Skolimowska. Int J Mol Sci. 2022 Sep 7;23(18):10341.
16. Akbari J et al. Pharm Biol. 2015;53(10):1442-7.
Used as a spice in various, particularly Mediterranean, cuisines and in traditional medicine for hundreds of years, this aromatic shrub has been the focus of substantial research this century to clarify its roles in skin care. It is used broadly in cosmetic formulations, particularly to preserve the product, and acts as a skin conditioner and fragrance in safe concentrations.1 Rosemary essential oil is also a popular choice frequently used in aromatherapy.2,3 This column focuses on recent promising results supporting the antioxidant and anti-photoaging activities, especially, of rosemary.
UV Protection and Rosemary in Combination
A 2021 study in mice authored by Auh and Madhavan showed that a mixture of marigold and rosemary extracts yielded anti-photoaging effects, with the botanical formula suppressing UV-induced damage.4
Seven years earlier, Pérez-Sánchez et al. combined rosemary and citrus extracts and found that they exerted protective effects against UV damage in human HaCaT keratinocytes as well as human volunteers after oral consumption. Significant increases in minimal erythema dose (MED) were seen in participants, with daily intake of 250 mg of botanical combination, at 8 weeks (34%) and 12 weeks (56%). The investigators attributed the photoprotective effects of the formula to rosemary polyphenols and diterpenes as well as citrus flavonoids.5
Evaluation of a human skin cell model by Sánchez-Marzo et al. in 2020 revealed that rosemary diterpenes were instrumental in an herbal extract that combined citrus, olive, and rosemary in conferring genoprotection against UV-induced DNA damage. The authors note that human trials are needed to overcome the limitations of the cellular model in ascertaining whether the tested herbal formulations can yield oral and/or topical photoprotection.6
Anti-Photoaging and Anti-Pollution
In 2022, Ibrahim et al. assessed a hexane extract of rosemary leaves for anti-photoaging activity. Their evaluation showed an abundance of triterpenoids, monoterpenoids, and phenolic diterpenes in rosemary, with in vitro assays verifying the anti-aging, antioxidant, and wound healing functions of the extract. Further, topical rosemary hexane extract–loaded lipid nanocapsules protected rat skin from UV radiation, as epidermal and dermal histological parameters improved, antioxidant biochemical balance was restored, and inflammatory markers and wrinkling were diminished. The researchers concluded that the use of rosemary hexane extract represents a safe, efficient, and cost-effective way to deliver anti-aging, photoprotective functions to cosmeceutical formulations.7
In March 2021, Nobile et al. published a report on their randomized, double-blind, placebo-controlled parallel group study to investigate the efficacy of a marketed polyphenol-enriched dietary supplement (Zeropollution, which contains four standardized herbal extracts: Olea europaea leaf, Lippia citriodora, S. rosmarinus, and Sophora japonica) in diminishing pollution-induced oxidative stress and in improving skin aging in 100 White and Asian women who were outdoor workers living in a polluted environment (Milan, Italy). Statistically significant improvements in reducing wrinkle depth and hyperpigmentation, enhancing elasticity and firmness, as well as promoting skin moisturization and diminishing transepidermal water loss were noted as early as 2 weeks after product consumption began, with inter-group and intra-group analysis verifying that all skin parameters were ameliorated in Asian and White subjects.8
Previously, Nobile et al. conducted a randomized, parallel-group study on 90 subjects to evaluate the photoprotective effects of a combination of rosemary and grapefruit (Citrus paradisi) extracts (Nutroxsun). The investigators also performed a pilot, randomized crossover study on five participants. Both studies included only females with Fitzpatrick skin phototypes I-III who manifested mild to moderate chronological aging or photoaging. Within as little as 2 weeks, treated individuals exhibited reductions in UVA- and UVB-induced skin changes. Skin elasticity improved in this group, with wrinkles diminishing along with skin redness and lipoperoxides. The investigators concluded that the oral blend of rosemary and grapefruit consumed long term merits consideration as an adjuvant approach to preventing the deleterious effects of solar exposure.9
In 2021, Hoskin et al. used ex vivo human biopsies exposed to diesel engine exhaust to study the impact of spray-dried algae-rosemary particles against pollution-induced damage. The spirulina-rosemary gel that was developed lowered levels of 4-hydroxynonenal protein adducts (4HNE-PA) as well as matrix metalloproteinase-9 (MMP-9) and reduced the loss of filaggrin. The researchers concluded that their topically applied spirulina-rosemary gel was effective in mitigating or preventing skin aging and cutaneous damage caused by diesel air pollution.10
Antioxidant, Antibacterial, and Anti-Inflammatory Activity
Based on a 2023 literature search by Li Pomi et al. of in vitro as well as in vivo animal and human studies involving S. rosmarinus and the skin, researchers reported on substantial evidence buttressing the antioxidant role of the botanical agent. They cautioned that, while data support the harnessing of the bioactive constituents of rosemary to address inflammatory and infectious skin conditions, large controlled trials remain necessary to establish its potential functions in dermatologic clinical practice.11
Ten years earlier, Park et al. determined that a phenolic diterpene from rosemary (carnosic acid) prevented UV-induced expression of MMP-1, MMP-3, and MMP-9 in human skin fibroblasts and keratinocytes in a concentration-dependent manner by suppressing reactive oxygen species and blocking through the inhibition of ROS and the suppression of extracellular signal-regulated kinase (ERK)-mediated AP-1 activation.12
Around the same time, Sienkiewicz et al. showed that rosemary essential oil exhibits antibacterial activity against the standard strain Escherichia coli ATCC 25922 and 60 other clinical strains of the bacteria.13
Further, anti-inflammatory properties have been attributed to rosemary essential oil, which are thought to be due to its suppression of nuclear factor kappa B transcription and inhibition of the arachidonic acid cascade.14
Other Functions of Rosemary
In 2022, Sutkowska-Skolimowska et al. demonstrated that rosemary extract in concentrations of 50 and 100mcg/mL significantly diminished accumulated collagen in the fibroblasts of four patients with severe and fatal osteogenesis imperfecta, suggesting that the botanical agent may have a role targeting cellular stress and inducing autophagy in therapy for this condition.15
In 2015, Akbari et al. established that 0.5% and 1% concentrations of rosemary essential oil were effective in facilitating the percutaneous absorption of diclofenac sodium topical gel.16
Conclusion
In Western culture, rosemary is thought of more as a spice to add flavor to food. However, there appears to be an emerging body of evidence suggesting various possible functions for rosemary in the dermatologic armamentarium. Much more research is necessary, though, to ascertain the most appropriate and optimal roles for this popular herb in skin care.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami, Florida. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a SaaS company used to generate skin care routines in office and as a ecommerce solution. Write to her at dermnews@mdedge.com.
References
1. González-Minero FJ et al. Cosmetics. 2020 Oct 3;7(4):77.
2. Sayorwan W et al. Sci Pharm. 2013 Apr-Jun;81(2):531-42.
3. Pazyar N et al. Skin Pharmacol Physiol. 2014;27(6):303-10.
4. Auh JH and Madhavan J Biomed Pharmacother. 2021 Mar;135:111178.
5. Pérez-Sánchez A et al. J Photochem Photobiol B. 2014 Jul 5;136:12-8.
6. Sánchez-Marzo N et al. Antioxidants (Basel). 2020 Mar 20;9(3):255.
7. Ibrahim N et al. Sci Rep. 2022 Jul 30;12(1):13102.
8. Nobile V et al. Food Nutr Res. 2021 Mar 29:65.
9. Nobile V et al. Food Nutr Res. 2016 Jul 1;60:31871.
10. Hoskin R et al. Molecules. 2021 Jun 22;26(13):3781.
11. Li Pomi F et al. Antioxidants (Basel). 2023 Mar 9;12(3):680.
12. Park M et al. Exp Dermatol. 2013 May;22(5):336-41.
13. Sienkiewicz M et al. Molecules. 2013 Aug 5;18(8):9334-51.
14. Borges RS et al. J Ethnopharmacol. 2019 Jan 30;229:29-45.
15. Sutkowska-Skolimowska. Int J Mol Sci. 2022 Sep 7;23(18):10341.
16. Akbari J et al. Pharm Biol. 2015;53(10):1442-7.