Blackberry

Endemic to Europe and North America, the blackberry (Rubus fruticosus) is naturally laden with an abundance of polyphenolic compounds, including ellagic acid, tannins, ellagitannins, quercetin, gallic acid, anthocyanins, and cyanidins, which have been associated with antioxidant and anticarcinogenic activity (J. Med. Food 2007;10:258-65; J. Agric. Food. Chem. 2002;50:3495-500; J. Agric. Food Chem. 2008;56:661-9). Indeed, the health benefits of consuming plants rich in anthocyanins have been known at least since the 1500s (Nat. Prod. Commun. 2011;6:149-56).

It is not surprising, then, that blackberries have long been part of traditional medicine. Rubus extracts have been used in traditional medicine for antimicrobial, anticonvulsant, and muscle relaxant indications, as well as for their ability to detect and inhibit free radicals (Int. J. Antimicrob. Agents. 2009;34:50-9). Rubus has been reported in traditional medicine on Sardinia for hemorrhoids, bleeding gums, and ulcers (J. Ethnobiol. Ethnomed. 2009;5:6). Phytotherapeutic uses have also been noted in Central Italy (Fitoterapia. 2005;76:1-25). Dermatologic applications of blackberry in southern Italy include use of the leaves to treat dog bites, and use of the roots in a hair-wash preparation (J. Ethnobiol. Ethnomed. 2008;4:5).

Data from other studies suggest additional potential uses for blackberry. For example, polyphenols and leaf extract of Rubus ulmifolius exhibited antibacterial activity against two strains of Helicobacter pylori (Int. J. Antimicrob. Agents. 2009;34:50-9). The antimicrobial activity of berries and other anthocyanin-containing fruits, which are typically more effective against Gram-positive than Gram-negative bacteria, is believed to result from various mechanisms and interactions associated with anthocyanins, weak organic acids, phenolic acids, and their mixtures of varying chemical composition (Nat. Prod. Commun. 2011;6:149-56; J. Ethnopharmacol. 2002;79:165-8).

Anti-inflammatory activity

In 2006, Pergola et al. examined whether the pharmacological activity of the anthocyanin fraction of a blackberry extract (cyanidin-3-O-glucoside, approximately 88% of the total anthocyanin content) could be attributed to the inhibition of nitric oxide production. The researchers found that the increased synthesis of nitrites spurred by the treatment of J774 cells with lipopolysaccharide over 24 hours was inhibited by anthocyanin, in a concentration-dependent manner. They concluded that the anti-inflammatory activity associated with blackberry extract can be partially ascribed to the blocking of nitric oxide synthesis by cyanidin-3-O-glucoside, the primary anthocyanin found in the extract (Nitric Oxide 2006;15:30-9).

In another study involving in vivo data and a mouse ear model, investigators assessed the antioxidant and topical anti-inflammatory activity of low- and high-molecular-weight phenolic fractions from three blackberry cultivars (i.e., Navaho, Kiowa, and Ouachita) bred for the warm and humid conditions of the southeastern United States. They found that all three formulations significantly mitigated TPA-induced inflammation. In addition, the researchers investigated mouse ear myeloperoxidase activity, an indicator of polymorphonuclear leukocyte infiltration, and noted that it was substantially diminished after topical application of both blackberry preparations as well as indomethacin (J. Agric. Food. Chem. 2010;58:6102-9).

Antioxidant activity

Blackberries consistently rank highly in oxygen radical absorbance capacity (ORAC), and they showed the strongest antioxidant activity among 1,000 antioxidant foods eaten in the United States in a study by Halvorsen et al. (Am. J. Clin. Nutr. 2006;84:95-135).

Investigators recently evaluated and compared the effect of extraction time (5 and 15 minutes) and hydrolysis on the qualitative and quantitative content of phenolic compounds and antioxidant capacity of six traditional medicinal plants, including blackberry (Rubus fruticosus), lemon balm (Melissa officinalis), thyme (Thymus serpyllum), lavender (Lavandula officinalis), stinging nettle (Urtica dioica), and olive (Olea europea). The distribution of phenolic compounds identified varied widely among the botanicals selected, and the extraction efficiency and antioxidant capacity of the extracts were influenced by prolonged extraction and hydrolysis. The hydrolyzed extract of blackberry leaves, obtained after 15 minutes of extraction, demonstrated the highest phenolic content and antioxidant capacity (Phytochem. Anal. 2011;22:172-80).

In 2007, Dai et al. obtained Hull blackberries grown in Kentucky and analyzed total anthocyanin and phenolic content, polymeric color, as well as anthocyanin composition and antioxidant capacity. Their in vitro cell culture work indicated that the blackberry extract suppressed HT-29 colon tumor cell growth by up to 66% after 72 hours, in a concentration-dependent manner. High-dose and low-dose lipid A-induced interleukin-12 release was also concentration-dependently inhibited from mouse bone marrow–derived dendritic cells by total anthocyanin concentrations (0-40 mcg/mL). The investigators concluded that the blackberry extract exhibits strong antioxidant, antiproliferative, and anti-inflammatory activities, and products based on the extract might be considered for the treatment or prevention of inflammatory conditions as well as cancer (J. Med. Food 2007;10:258-65).

Anticarcinogenic activity

In 2004, Feng et al. studied the effects of fresh blackberry extracts on cancer cell proliferation and neoplastic transformation induced by TPA. They confirmed, using electron spin resonance, that the extract effectively scavenges hydroxyl and superoxide free radicals. They also determined that pretreatment of the human cancer cell line A549 with blackberry extract suppressed cell proliferation and inhibited 8-hydroxy-2\'-deoxyguanosine (8-OHdG) formation induced by UVB. In addition, pretreatment with the extract reduced neoplastic transformation of JB6 P+ cells induced by TPA and blocked UVB- and TPA-induced AP-1 transactivation. The investigators concluded that fresh blackberry extract appears to have anticarcinogenic properties, and that associated activity may be derived from its antioxidant characteristics (Nutr. Cancer 2004;50:80-9).

In 2006, Ding et al. examined the chemopreventive and chemotherapeutic activity of cyanidin-3-glucoside (C3G), a key active ingredient in blackberry. C3G was shown to scavenge UVB-induced hydroxyl and superoxide radicals in cultured JB6 cells. The investigators observed reductions in the number of nonmalignant and malignant skin tumors per mouse induced by TPA in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. In addition, UVB- and TPA-induced transactivation of NF-kappaB and AP-1 and expression of cyclooxygenase-2 and tumor necrosis factor–alpha were suppressed by the pretreatment with C3G of JB6 cells. The researchers suggested that the inhibition of MAPK activity may be important in mediating such effects. TPA-induced neoplastic transformation in JB6 cells was also hindered via C3G pretreatment. Further, C3G suppressed proliferation of the human lung carcinoma cell line A549, diminished the size of A549 tumor xenograft growth, and significantly limited metastasis in nude mice. The investigators concluded that C3G, an important constituent of blackberry, displays significant anticancer activity by dint of its capacity to scavenge free radicals. As such, they suggested that this blackberry derivative, which exhibits scant cytotoxicity to healthy tissue, warrants additional study as a preventive and therapeutic agent in human cancers (J. Biol. Chem. 2006;281:17359-68).

Conclusion

The most recent evidence suggests that blackberry warrants attention for medical applications, including dermatology. In fact, in a small (n = 33) single-center, open-label study led by the author, significant improvement in most metrics of photoaged skin was observed after the use of a day and night regimen containing blackberry leaf extract, dill extract, and Zn-Cu(II) bi-mineral complex in patients with mild to moderate photodamage. (Baumann LS, Figueras KA, Bell M, Flitter CJ. Assessing the efficacy and tolerance of a day and night regimen containing blackberry leaf extract, dill extract, and Cu-Zinc bi-mineral complex in subjects with mild to moderate photoaged skin. Unpublished results.) It remains to be seen if and when blackberry extract alone may be harnessed for dermatologic indications, but present data are promising, and justify continued study.

Dr. Baumann is in private practice in Miami Beach. She did not disclose any conflicts of interest. To respond to this column, or to suggest topics for future columns, write to her at sknews@frontlinemedcom.com.

Endemic to Europe and North America, the blackberry (Rubus fruticosus) is naturally laden with an abundance of polyphenolic compounds, including ellagic acid, tannins, ellagitannins, quercetin, gallic acid, anthocyanins, and cyanidins, which have been associated with antioxidant and anticarcinogenic activity (J. Med. Food 2007;10:258-65; J. Agric. Food. Chem. 2002;50:3495-500; J. Agric. Food Chem. 2008;56:661-9). Indeed, the health benefits of consuming plants rich in anthocyanins have been known at least since the 1500s (Nat. Prod. Commun. 2011;6:149-56).

It is not surprising, then, that blackberries have long been part of traditional medicine. Rubus extracts have been used in traditional medicine for antimicrobial, anticonvulsant, and muscle relaxant indications, as well as for their ability to detect and inhibit free radicals (Int. J. Antimicrob. Agents. 2009;34:50-9). Rubus has been reported in traditional medicine on Sardinia for hemorrhoids, bleeding gums, and ulcers (J. Ethnobiol. Ethnomed. 2009;5:6). Phytotherapeutic uses have also been noted in Central Italy (Fitoterapia. 2005;76:1-25). Dermatologic applications of blackberry in southern Italy include use of the leaves to treat dog bites, and use of the roots in a hair-wash preparation (J. Ethnobiol. Ethnomed. 2008;4:5).

Data from other studies suggest additional potential uses for blackberry. For example, polyphenols and leaf extract of Rubus ulmifolius exhibited antibacterial activity against two strains of Helicobacter pylori (Int. J. Antimicrob. Agents. 2009;34:50-9). The antimicrobial activity of berries and other anthocyanin-containing fruits, which are typically more effective against Gram-positive than Gram-negative bacteria, is believed to result from various mechanisms and interactions associated with anthocyanins, weak organic acids, phenolic acids, and their mixtures of varying chemical composition (Nat. Prod. Commun. 2011;6:149-56; J. Ethnopharmacol. 2002;79:165-8).

Anti-inflammatory activity

In 2006, Pergola et al. examined whether the pharmacological activity of the anthocyanin fraction of a blackberry extract (cyanidin-3-O-glucoside, approximately 88% of the total anthocyanin content) could be attributed to the inhibition of nitric oxide production. The researchers found that the increased synthesis of nitrites spurred by the treatment of J774 cells with lipopolysaccharide over 24 hours was inhibited by anthocyanin, in a concentration-dependent manner. They concluded that the anti-inflammatory activity associated with blackberry extract can be partially ascribed to the blocking of nitric oxide synthesis by cyanidin-3-O-glucoside, the primary anthocyanin found in the extract (Nitric Oxide 2006;15:30-9).

In another study involving in vivo data and a mouse ear model, investigators assessed the antioxidant and topical anti-inflammatory activity of low- and high-molecular-weight phenolic fractions from three blackberry cultivars (i.e., Navaho, Kiowa, and Ouachita) bred for the warm and humid conditions of the southeastern United States. They found that all three formulations significantly mitigated TPA-induced inflammation. In addition, the researchers investigated mouse ear myeloperoxidase activity, an indicator of polymorphonuclear leukocyte infiltration, and noted that it was substantially diminished after topical application of both blackberry preparations as well as indomethacin (J. Agric. Food. Chem. 2010;58:6102-9).

Antioxidant activity

Blackberries consistently rank highly in oxygen radical absorbance capacity (ORAC), and they showed the strongest antioxidant activity among 1,000 antioxidant foods eaten in the United States in a study by Halvorsen et al. (Am. J. Clin. Nutr. 2006;84:95-135).

Investigators recently evaluated and compared the effect of extraction time (5 and 15 minutes) and hydrolysis on the qualitative and quantitative content of phenolic compounds and antioxidant capacity of six traditional medicinal plants, including blackberry (Rubus fruticosus), lemon balm (Melissa officinalis), thyme (Thymus serpyllum), lavender (Lavandula officinalis), stinging nettle (Urtica dioica), and olive (Olea europea). The distribution of phenolic compounds identified varied widely among the botanicals selected, and the extraction efficiency and antioxidant capacity of the extracts were influenced by prolonged extraction and hydrolysis. The hydrolyzed extract of blackberry leaves, obtained after 15 minutes of extraction, demonstrated the highest phenolic content and antioxidant capacity (Phytochem. Anal. 2011;22:172-80).

In 2007, Dai et al. obtained Hull blackberries grown in Kentucky and analyzed total anthocyanin and phenolic content, polymeric color, as well as anthocyanin composition and antioxidant capacity. Their in vitro cell culture work indicated that the blackberry extract suppressed HT-29 colon tumor cell growth by up to 66% after 72 hours, in a concentration-dependent manner. High-dose and low-dose lipid A-induced interleukin-12 release was also concentration-dependently inhibited from mouse bone marrow–derived dendritic cells by total anthocyanin concentrations (0-40 mcg/mL). The investigators concluded that the blackberry extract exhibits strong antioxidant, antiproliferative, and anti-inflammatory activities, and products based on the extract might be considered for the treatment or prevention of inflammatory conditions as well as cancer (J. Med. Food 2007;10:258-65).

Anticarcinogenic activity

In 2004, Feng et al. studied the effects of fresh blackberry extracts on cancer cell proliferation and neoplastic transformation induced by TPA. They confirmed, using electron spin resonance, that the extract effectively scavenges hydroxyl and superoxide free radicals. They also determined that pretreatment of the human cancer cell line A549 with blackberry extract suppressed cell proliferation and inhibited 8-hydroxy-2\'-deoxyguanosine (8-OHdG) formation induced by UVB. In addition, pretreatment with the extract reduced neoplastic transformation of JB6 P+ cells induced by TPA and blocked UVB- and TPA-induced AP-1 transactivation. The investigators concluded that fresh blackberry extract appears to have anticarcinogenic properties, and that associated activity may be derived from its antioxidant characteristics (Nutr. Cancer 2004;50:80-9).

In 2006, Ding et al. examined the chemopreventive and chemotherapeutic activity of cyanidin-3-glucoside (C3G), a key active ingredient in blackberry. C3G was shown to scavenge UVB-induced hydroxyl and superoxide radicals in cultured JB6 cells. The investigators observed reductions in the number of nonmalignant and malignant skin tumors per mouse induced by TPA in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. In addition, UVB- and TPA-induced transactivation of NF-kappaB and AP-1 and expression of cyclooxygenase-2 and tumor necrosis factor–alpha were suppressed by the pretreatment with C3G of JB6 cells. The researchers suggested that the inhibition of MAPK activity may be important in mediating such effects. TPA-induced neoplastic transformation in JB6 cells was also hindered via C3G pretreatment. Further, C3G suppressed proliferation of the human lung carcinoma cell line A549, diminished the size of A549 tumor xenograft growth, and significantly limited metastasis in nude mice. The investigators concluded that C3G, an important constituent of blackberry, displays significant anticancer activity by dint of its capacity to scavenge free radicals. As such, they suggested that this blackberry derivative, which exhibits scant cytotoxicity to healthy tissue, warrants additional study as a preventive and therapeutic agent in human cancers (J. Biol. Chem. 2006;281:17359-68).

Conclusion

The most recent evidence suggests that blackberry warrants attention for medical applications, including dermatology. In fact, in a small (n = 33) single-center, open-label study led by the author, significant improvement in most metrics of photoaged skin was observed after the use of a day and night regimen containing blackberry leaf extract, dill extract, and Zn-Cu(II) bi-mineral complex in patients with mild to moderate photodamage. (Baumann LS, Figueras KA, Bell M, Flitter CJ. Assessing the efficacy and tolerance of a day and night regimen containing blackberry leaf extract, dill extract, and Cu-Zinc bi-mineral complex in subjects with mild to moderate photoaged skin. Unpublished results.) It remains to be seen if and when blackberry extract alone may be harnessed for dermatologic indications, but present data are promising, and justify continued study.

Dr. Baumann is in private practice in Miami Beach. She did not disclose any conflicts of interest. To respond to this column, or to suggest topics for future columns, write to her at sknews@frontlinemedcom.com.

Endemic to Europe and North America, the blackberry (Rubus fruticosus) is naturally laden with an abundance of polyphenolic compounds, including ellagic acid, tannins, ellagitannins, quercetin, gallic acid, anthocyanins, and cyanidins, which have been associated with antioxidant and anticarcinogenic activity (J. Med. Food 2007;10:258-65; J. Agric. Food. Chem. 2002;50:3495-500; J. Agric. Food Chem. 2008;56:661-9). Indeed, the health benefits of consuming plants rich in anthocyanins have been known at least since the 1500s (Nat. Prod. Commun. 2011;6:149-56).

It is not surprising, then, that blackberries have long been part of traditional medicine. Rubus extracts have been used in traditional medicine for antimicrobial, anticonvulsant, and muscle relaxant indications, as well as for their ability to detect and inhibit free radicals (Int. J. Antimicrob. Agents. 2009;34:50-9). Rubus has been reported in traditional medicine on Sardinia for hemorrhoids, bleeding gums, and ulcers (J. Ethnobiol. Ethnomed. 2009;5:6). Phytotherapeutic uses have also been noted in Central Italy (Fitoterapia. 2005;76:1-25). Dermatologic applications of blackberry in southern Italy include use of the leaves to treat dog bites, and use of the roots in a hair-wash preparation (J. Ethnobiol. Ethnomed. 2008;4:5).

Data from other studies suggest additional potential uses for blackberry. For example, polyphenols and leaf extract of Rubus ulmifolius exhibited antibacterial activity against two strains of Helicobacter pylori (Int. J. Antimicrob. Agents. 2009;34:50-9). The antimicrobial activity of berries and other anthocyanin-containing fruits, which are typically more effective against Gram-positive than Gram-negative bacteria, is believed to result from various mechanisms and interactions associated with anthocyanins, weak organic acids, phenolic acids, and their mixtures of varying chemical composition (Nat. Prod. Commun. 2011;6:149-56; J. Ethnopharmacol. 2002;79:165-8).

Anti-inflammatory activity

In 2006, Pergola et al. examined whether the pharmacological activity of the anthocyanin fraction of a blackberry extract (cyanidin-3-O-glucoside, approximately 88% of the total anthocyanin content) could be attributed to the inhibition of nitric oxide production. The researchers found that the increased synthesis of nitrites spurred by the treatment of J774 cells with lipopolysaccharide over 24 hours was inhibited by anthocyanin, in a concentration-dependent manner. They concluded that the anti-inflammatory activity associated with blackberry extract can be partially ascribed to the blocking of nitric oxide synthesis by cyanidin-3-O-glucoside, the primary anthocyanin found in the extract (Nitric Oxide 2006;15:30-9).

In another study involving in vivo data and a mouse ear model, investigators assessed the antioxidant and topical anti-inflammatory activity of low- and high-molecular-weight phenolic fractions from three blackberry cultivars (i.e., Navaho, Kiowa, and Ouachita) bred for the warm and humid conditions of the southeastern United States. They found that all three formulations significantly mitigated TPA-induced inflammation. In addition, the researchers investigated mouse ear myeloperoxidase activity, an indicator of polymorphonuclear leukocyte infiltration, and noted that it was substantially diminished after topical application of both blackberry preparations as well as indomethacin (J. Agric. Food. Chem. 2010;58:6102-9).

Antioxidant activity

Blackberries consistently rank highly in oxygen radical absorbance capacity (ORAC), and they showed the strongest antioxidant activity among 1,000 antioxidant foods eaten in the United States in a study by Halvorsen et al. (Am. J. Clin. Nutr. 2006;84:95-135).

Investigators recently evaluated and compared the effect of extraction time (5 and 15 minutes) and hydrolysis on the qualitative and quantitative content of phenolic compounds and antioxidant capacity of six traditional medicinal plants, including blackberry (Rubus fruticosus), lemon balm (Melissa officinalis), thyme (Thymus serpyllum), lavender (Lavandula officinalis), stinging nettle (Urtica dioica), and olive (Olea europea). The distribution of phenolic compounds identified varied widely among the botanicals selected, and the extraction efficiency and antioxidant capacity of the extracts were influenced by prolonged extraction and hydrolysis. The hydrolyzed extract of blackberry leaves, obtained after 15 minutes of extraction, demonstrated the highest phenolic content and antioxidant capacity (Phytochem. Anal. 2011;22:172-80).

In 2007, Dai et al. obtained Hull blackberries grown in Kentucky and analyzed total anthocyanin and phenolic content, polymeric color, as well as anthocyanin composition and antioxidant capacity. Their in vitro cell culture work indicated that the blackberry extract suppressed HT-29 colon tumor cell growth by up to 66% after 72 hours, in a concentration-dependent manner. High-dose and low-dose lipid A-induced interleukin-12 release was also concentration-dependently inhibited from mouse bone marrow–derived dendritic cells by total anthocyanin concentrations (0-40 mcg/mL). The investigators concluded that the blackberry extract exhibits strong antioxidant, antiproliferative, and anti-inflammatory activities, and products based on the extract might be considered for the treatment or prevention of inflammatory conditions as well as cancer (J. Med. Food 2007;10:258-65).

Anticarcinogenic activity

In 2004, Feng et al. studied the effects of fresh blackberry extracts on cancer cell proliferation and neoplastic transformation induced by TPA. They confirmed, using electron spin resonance, that the extract effectively scavenges hydroxyl and superoxide free radicals. They also determined that pretreatment of the human cancer cell line A549 with blackberry extract suppressed cell proliferation and inhibited 8-hydroxy-2\'-deoxyguanosine (8-OHdG) formation induced by UVB. In addition, pretreatment with the extract reduced neoplastic transformation of JB6 P+ cells induced by TPA and blocked UVB- and TPA-induced AP-1 transactivation. The investigators concluded that fresh blackberry extract appears to have anticarcinogenic properties, and that associated activity may be derived from its antioxidant characteristics (Nutr. Cancer 2004;50:80-9).

In 2006, Ding et al. examined the chemopreventive and chemotherapeutic activity of cyanidin-3-glucoside (C3G), a key active ingredient in blackberry. C3G was shown to scavenge UVB-induced hydroxyl and superoxide radicals in cultured JB6 cells. The investigators observed reductions in the number of nonmalignant and malignant skin tumors per mouse induced by TPA in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. In addition, UVB- and TPA-induced transactivation of NF-kappaB and AP-1 and expression of cyclooxygenase-2 and tumor necrosis factor–alpha were suppressed by the pretreatment with C3G of JB6 cells. The researchers suggested that the inhibition of MAPK activity may be important in mediating such effects. TPA-induced neoplastic transformation in JB6 cells was also hindered via C3G pretreatment. Further, C3G suppressed proliferation of the human lung carcinoma cell line A549, diminished the size of A549 tumor xenograft growth, and significantly limited metastasis in nude mice. The investigators concluded that C3G, an important constituent of blackberry, displays significant anticancer activity by dint of its capacity to scavenge free radicals. As such, they suggested that this blackberry derivative, which exhibits scant cytotoxicity to healthy tissue, warrants additional study as a preventive and therapeutic agent in human cancers (J. Biol. Chem. 2006;281:17359-68).

Conclusion

The most recent evidence suggests that blackberry warrants attention for medical applications, including dermatology. In fact, in a small (n = 33) single-center, open-label study led by the author, significant improvement in most metrics of photoaged skin was observed after the use of a day and night regimen containing blackberry leaf extract, dill extract, and Zn-Cu(II) bi-mineral complex in patients with mild to moderate photodamage. (Baumann LS, Figueras KA, Bell M, Flitter CJ. Assessing the efficacy and tolerance of a day and night regimen containing blackberry leaf extract, dill extract, and Cu-Zinc bi-mineral complex in subjects with mild to moderate photoaged skin. Unpublished results.) It remains to be seen if and when blackberry extract alone may be harnessed for dermatologic indications, but present data are promising, and justify continued study.

Dr. Baumann is in private practice in Miami Beach. She did not disclose any conflicts of interest. To respond to this column, or to suggest topics for future columns, write to her at sknews@frontlinemedcom.com.