“Phytochemical Profile and Pharmacological Potential of Borago officinalis: Mechanistic and Therapeutic Insights”

1.1 Botanical Profile and Taxonomy

1.2 Botanical Description

Borago officinalis: An annual herbaceous plant with prominent hairs, and with a generally rough or hispid surface (6). The flowers are pentamerous, bisexual and the leaves are simple, alternate. Its distinctive flowers are borne in cymose inflorescences, and are frequently blue (7).

1.3 Geographical Distribution and Habitat

Borago officinalis grows in the western and central Mediterranean region, in Spain, Portugal, France, Italy, Greece, Morocco, Algeria, Tunisia and Libya (8). Since then, it has been imported and naturalised in a number of areas outside of its original range (9). It can grow in disturbed habitats, cultivated areas and other appropriate locations, but it is primarily found in temperate climates (10).

1.4 Common Names and Traditional Importance

It is also referred to as starflower or borage and has been utilized for food and medicine for a long time. Historically, many parts of the plant have been exploited for various purposes, but borage seed oil is particularly interesting because of its relative richness in gamma-linolenic acid (GLA), a fatty acid (11).

Phytochemical Constituents

2. Pharmacological activity

2.1 Antioxidant activity

Borago officinalis seedcake extract, made using 50% ethanol at 50°C for 48 hours, has a high phenolic content and a strong antioxidant activity. It is used as a natural ingredient in food, medicine, cosmetics, and agriculture. Antioxidant supplements. The antioxidant impact was assessed with 2,2'-azino-bis (3- 2,2-Diphenyl-1-picrylhydrazyl (ABTS) and ethylbenzothiazoline-6-sulfonic acid (ABTS)(12). Using the ferric reducing and DPPH techniques, borage essential oil (13) and flavonoid extract demonstrated antioxidant properties.. This activity seems to be high for the borage flavonoids and low for the essential oil. Ferric ion (Fe3+) reducing power (FRAP), ferrous ion (Fe2+) metal chelating, and DPPH were among the methods used to assess the antioxidant capacity of the borage flowers' methanolic crude extract and its partitions. Peroxidase (POX) and catalase (CAT) activities were used to exclude hydrogen peroxide (H2O2). Borage extracts' strong antioxidant potential is ascribed to their capacity to scavenge various reactive oxygen species (ROS) and prevent peroxidation. These extracts have active components that react with free radicals to scavenge potential harm (CAT and POX (13). DPPH, the FRAP assay, and Folin's technique (which measures the concentration of polyphenolics) were used to assess the antioxidant impact of borage leaves and flowers. Borage flowers contained more polyphenols and had a greater capacity to reduce ferric acid than leaves. Furthermore, the flowers had a larger residual unreduced DPPH radical concentration. A comparison of the wild and cultivated borage species' antioxidant capacities showed that the wild species had more activity and a higher polyphenolic concentration. Due to the higher solubility of the phenolics in ethanol, a comparative investigation revealed that using ethanol as a diluent had stronger antioxidant and superoxide scavenging capability than distilled water (14). The strong antioxidant action of this species was described in 2019 when about ten flavonoids were discovered in the extract of borage leaves (15).

2.2 Antimicrobial Act

Because of its strong antibacterial properties, borage may be used to treat infections. The phytochemical analysis of the essential oils and flavonoid extracts reveals that the primary constituent of the essential oils is spathulenol, whilst the flavonoids are rutin and quercetin. Spathulenol's chemical structure. Because both extracts contain antibacterial components, the borage extract's flavonoids have a greater antimicrobial effect than the essential oil. The extracted spathulenol from the essential oil extract has little antibacterial activity; it is more commonly thought of as an antifungal agent. Rutin and quercetin are regarded as antibacterial substances. Unlike flavonoids, which exhibit activity against both types of bacteria, this plant's essential oils exhibit greater activity against Gram-negative than Gram-positive bacteria, and extended activity against resistant respiratory strains (16). In another study, the aqueous extract (AE) from borage leaves showed varying degrees of antibacterial activity against Staphylococci and Enterobacteria. The AE had modest effectiveness against Salmonella enterica but no bacterial inhibition against Listeria monocytogenes (17). Distilled water, ethanol, and methanol were the different solvents used to extract the borage flower metabolites that showed the antibacterial effect. Compared to ethanol and distilled water, the methanol extract has a greater antibacterial ability because it contains more flavonoids. Borage extracts are thought to be a promising source of natural antimicrobials and may help with medication and food preservation. Bacillus cereus was the most susceptible strain of Gram-negative bacteria, whereas Micrococcus luteus was the most resistant (18). Escherichia coli was the most sensitive Gram-negative bacterium, whereas Pseudomonas aeruginosa was the most resistant. Flavonoids, fatty acids, and other polyphenolics were linked to the antibacterial properties of the borage flower extracts. According to other research, borage leaf extracts demonstrated antibacterial efficacy against a number of pathogens, including Bacillus subtilis, Salmonella enterica, Staphylococcus aureus, and Listeria (19). Due to markedly increased mononuclear cell counts at the wound site, Borago officinalis's wound-healing activity can aid in the healing process. These characteristics may be caused by phenolic compounds present in the hydroethanolic extract, and these cellular alterations indicate the beginning of the proliferative phase and the reduction of the inflammatory phase (20).

2.3 Hepatoprotective Activity

In rat liver models, the BSO demonstrated hepatoprotective efficacy against disruptions caused by gamma (γ-) radiation. The lipid profile, serum liver enzyme levels, hepatic and serum malondialdehyde (MDA), and reduced glutathione (GSH) levels were all considerably improved by oral BSO therapy (21). Radiation exposure is linked to the notable drop in hepatic and serum levels of reduced glutathione (GSH) and a rise in hepatic and serum levels of malondialdehyde (MDA). The interaction between polyunsaturated fatty acids and free radicals in the phospholipid section of cellular membranes may be the cause of the increased MDA levels. The oxidative stress caused by ionising radiation may be the cause of the decreased levels of GSH. Hepatic GSH levels significantly increased, and hepatic MDA significantly decreased in rats exposed to γ-radiation and treated with borage (22). Increased serum enzymatic activity of gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) following γirradiation exposure may indicate the presence of liver damage. Damage to the liver membrane could be the cause of the rise in liver enzyme levels. Oral borage administration effectively reduced the rising blood biomarker levels of ALT, GGT, and AST when hepatobiliary damage, intrahepatic and extrahepatic bile flow impairment, or erythrocyte destruction triggered by radiation were present. Borage's potential as a strong antioxidant to inhibit hepatic damage by preserving plasma membrane integrity and so preventing the enzymes from leaking into the blood may be the reason for the notable drop in liver enzyme levels following borage intake (23).

2.4 Hypoglycemic Activity

In a rat model of alloxan-induced diabetes, a methanolic extract made by Soxhletting B. officinalis demonstrated hypoglycemic qualities (24). The plant under research is high in GLA, which is used as a medication to treat a variety of conditions, including multiple sclerosis, diabetes, heart disease, arthritis, local eczema, and cyclical mastalgia (25). Anti-inflammatory action: Inflammation is a natural defensive reaction triggered by infection or tissue damage that helps the body fight off intruders (microorganisms and other objects) and eliminate damaged or dead host cells. development of inflammatory diseases is significantly influenced by the overproduction of pro-inflammatory mediators and cytokines, including tumour necrosis factor-α, interleukin-6 (IL-6), IL-1, prostaglandin E2 (PGE2), and nitric oxide (NO). By preventing prostaglandin (PG) synthesis and reducing the activities of cyclooxygenase-1 (Cox1) and Cox 2, anti-inflammatory drugs lessen inflammation and pain. enzyme. The lipopolysaccharide (LPS)/gamma interferon (INF-γ)-induced murine macrophage cell line 264.7 was used to assess the anti-inflammatory effects of aqueous, ethanolic, and methanolic borage extracts (26). The presence of phenolic compounds was linked to the low anti-inflammatory impact of borage flower extracts in murine RAW 264.7 macrophage cells. Similar to nitro-L-arginine methyl ester (L-NAME) as an anti-inflammatory drug, the ethanolic and methanolic extracts may inhibit the synthesis of nitric oxide (27).

2.5 Antithrombotic Activity

GLA demonstrates antithrombotic effects by suppressing platelet clumping and lowering thromboxane synthesis (28). In one study that compared borage oil with evening primrose oil, borage oil was shown to have a stronger impact on suppressing thromboxane B2levels and platelet activation, which points to its greater capacity to ease hypercoagulable conditions (29). This antithrombotic mechanism is vital for averting cardiovascular incidents such as myocardial infarction and stroke, especially in individuals with preexisting metabolic disorders (30).

Extraction

Supercritical fluid extraction

For borage seed extraction, the effects of varying CO2 pressures and the addition of caprylic acid methyl ester as an entrainer were investigated. The extract yield increased from 0.14 to 24.29% (w/w) when the CO2 pressure was raised from 100 to 350 bar, although the extract composition did not significantly change. Pure caprylic acid methyl ester was found to be most soluble in dense CO2 at 100 and 300 bar (about 1 g of ester in 1 g of CO2). The yield of pure extract rose by up to 47.8 times at 100 bar and 2.4 times at 200 and 300 bar when this entrainer was added. Because caprylic acid methyl ester is very soluble at lower pressures (100 bar).

Extraction by compressed CO2

CO2 The extraction of borage seed oil using compressed CO2 was studied on a pilot plant apparatus with the aim of optimising plant performance and collecting data for scale-up purposes. The seeds were pre-treated by flaking them Volume 5, Issue 1, November – December 2010; Article-005 ISSN 0976 – 044X International Journal of Pharmaceutical Sciences Review and Research. 0.3 mm flakes before the extraction experiments to achieve quantitative oil recovery. The effects of temperature (10–55 °C), extraction pressure (200–300 bar), solvent flow rate (7.5–12 kg/h), and bed length (0.25–0.50 m) were investigated (31). Up until 70% of the oil was extracted, oil solubility in CO2 was a significant factor in controlling the extraction rate. After that, the rate at which the residual oil was extracted appeared to have been determined by intraparticle resistances (32). The experimental data were correlated using a mathematical model based on the fact that the oil is partially exposed to solvent following the pre-treatment of the seed. The calculated and observed oil yields differed by an average of 8%. The solid phase mass transfer coefficient (ks), specific interfacial area (a), and fraction of freely accessible oil (fk) all had best-fitting values of 0.7, 2.8 × 10−7 m/s, and 350 m −1, respectively (33)

Chromatography

GC-MS

When subjected to capillary gas chromatography, picolinyl ester derivatives of fatty acids were shown to have as good chromatographic properties as the corresponding methyl esters. By using a capillary column of medium polarity (Supelcowax 10), excellent resolution with respect to chain length, degree of unsaturation and positional isomers was obtained without any serious problems with a disturbed background due to column bleed in the mass spectrometric interpretation of fatty acids with respect to molecular weight, number of double bonds and positional isomers. The usefulness of the technique for the identification of the fatty acids in borage seed oil (Borago officinalis) was demonstrated. In addition to γ-linolenic acid, the most important fatty acid in borage seed oil from a commercial standpoint, a further fourteen different fatty acids could be positively identified (34). Gas chromatography–mass spectrometry analysis of seed Borago officinalis essential oil (EO) revealed the presence of 16 volatile components. β-Caryophyllene (26%) and p-cymene-8-ol (19.7%) represented the major components, while nonadecane (0.7%) and hexanol (0.7%) were the minor ones (35). The EO composition was characterised by a higher abundance of oxygenated monoterpenes (27.7%), followed by sesquiterpenes (26%)(36). Fatty acid composition showed the predominance of linoleic (35.4%), oleic (24.2%) and γ-linolenic (20.4%) acids (37). Polyphenols were analysed by reversed-phase high-performance liquid chromatography after acid hydrolysis of phenolic acid esters. Six phenolic acids were identified in seed extract, and rosmarinic acid was the predominant one with 1.65 mg/g dry matter weight equivalent to 33% of total phenolic acids. These features allowed a simple one-step procedure for characterising phenolic acids (38).

CONCLUSION

This review examines the hepatoprotective, antispasmodic, bronchodilator, vasodilator, cardio-depressant, anxiolytic, antioxidant, antibacterial, anti-inflammatory, and anticancer properties of Gaozaban (39). This validates its therapeutic use in the Unani system of medicine for various ailments (40). Numerous phytochemicals, including fatty acids, alkaloids, glycosides, saponins, flavonoids, resins, and allantoin, are responsible for the aforementioned pharmacological properties. Further research on Gaozaban's pharmacological properties and mechanism of action is crucial for drug discovery, given its claimed activity (41).

REFERENCES

1. Asadi-Samani M, Bahmani M, Rafieian-Kopaei M. The chemical composition, botanical characteristics, and biological activities of Borago officinalis: A review. Asian Pacific Journal of Tropical Medicine. 2014;7 (Supply 1):S22–S28. doi:10.1016/S1995-7645 (14)60200-2.
2. Gilani AH, Bashir S, Khan A. Pharmacological basis for the use of Borago officinalis in gastrointestinal, respiratory and cardiovascular disorders. Journal of Ethnopharmacology. 2007;114 (3):393–399. doi:10.1016/j.jep.2007.08.032.
3. Guil-Guerrero JL, Gómez-Mercado F, Rodríguez-García I. Occurrence and characterisation of oils rich in γ-linolenic acid. I: Higher plants from SE Spain. Phytochemistry. 2001;57 (3):409–415. doi:10.1016/S0031-9422 (01)00049-9.
4. Zadernowski R, Naczk M, Czaplicki S. Chemical composition of borage (Borago officinalis L.) seeds. Journal of Food Lipids. 2002;9 (4):289–300. doi:10.1111/j.1745-4522.2002.tb00226.x.
5. Larson et al. (1984) and Lüthy et al. (1984). Studies characterising pyrrolizidine alkaloids in Borago officinalis. Complete publication details should be verified from the sources before submission.
6. Ibrahim RM, Alshammaa DAS. Pharmacological aspects of Borago officinalis (Borage): A review article. Iraqi Journal of Pharmaceutical Sciences. 2023;32 (1):1–13. doi:10.31351/vol32iss1pp1-13.
7. Aliakbarlu et al. (2014). Study of the antioxidant and anti-inflammatory activities of borage flower extracts. Complete publication details should be verified from the source.
8. Ratz-Łyko et al. (2014). Research on the biological activities of borage extracts. Complete publication details should be verified from the source.
9. Mansour et al. (2014). Research on the radioprotective, antioxidant, and hepatoprotective effects of borage seed oil. Complete publication details should be verified from the source.
10. Lu et al. (2007). Research on extracting borage seed oil using compressed carbon dioxide. Complete publication details should be verified from the source.
11. Mhamdi et al. (2009). Research on the chemical composition of Borago officinalis seed essential oil and its volatile constituents. Complete publication details should be verified from the source.
12. Schramm et al. (2019). Review of the toxicological profiles and distribution of pyrrolizidine alkaloids in food crops. Complete publication details should be verified from the source.
13. Kapoor, R., & Huang, Y. S. (2006). Gamma-linolenic acid: An overview. In Y. S. Huang & V. A. Ziboh (Eds.), $\gamma$-Linolenic Acid: Recent Advances in Biotechnology and Clinical Applications (pp. 1–13). AOCS Press. https://doi.org/10.1201/9781439822364
14. Zadernowski, R., Naczk, M., & Czaplicki, S. (2002). Chemical composition of borage (Borago officinalis L.) seeds. Journal of Food Lipids, 9 (4), 289–300. https://doi.org/10.1111/j.1745-4522.2002.tb00226.x
15. Zanetti, F., Vamerali, T., & Mosca, G. (2013). Yield and oil quality of borage (Borago officinalis L.) grown in North-East Italy. Industrial Crops and Products, 43, 209–214. https://doi.org/10.1016/j.indcrop.2012.07.019 (Focuses specifically on agricultural yield, lipid profiling, and economic production factors).
16. Review & Underlying Study: Comprehensive overview by Ibrahim & Alshammaa (2023)
17. Documented in flower phytopharmacology studies and reviewed in detail by Ibrahim & Alshammaa (2023) and Moliner et al. (2022).
18. Detailed in the comparative pharmacology review by Ibrahim & Alshammaa (2023) and original phytochemistry evaluations (e.g., Ghaly et al., 2015).
19. Ratz-Łyko et al. (2014) and Fernández-López et al. (2018).
20. Synthesised by Ibrahim & Alshammaa (2023); underlying bioassay screening data from Joshi et al. (2019) / Aliakbarlu et al. (2014).
21. Ratz-Łyko et al. (2014) and Zemmouri et al. (2019).
22. Naderi et al. (2012) / Asadi-Samani et al. (2014).
23.  El-Bahr et al. (2021) / Mansour et al. (2014) investigated the radioprotective and antioxidant properties of borage seed oil against whole-body gamma irradiation in rats.
24.  Synthesising Review: Documented in the hepatoprotection section of Ibrahim & Alshammaa (2023).
25. : Mansour et al. (2014).
26. Mansour et al. (2014) / El-Bahr et al. (2021).
27.  Kasture et al. (2009) / Naderi et al. (2012).
28.  Review Attribution: Synthesised in the hypoglycemic activity section of Ibrahim & Alshammaa (2023) and Kumari et al. (2023).
29.  Kapoor, R., & Huang, Y. S. (2006). Gamma-linolenic acid: An overview. $\gamma$-Linolenic Acid: Recent Advances in Biotechnology and Clinical Applications, 1–13.  Horrobin, D. F. (1992). Nutritional and medical importance of gamma-linolenic acid. Progress in Lipid Research, 31 (2), 163–194.
30. Overview section in Ibrahim & Alshammaa (2023).
31.  Aliakbarlu et al. (2014) investigated the anti-inflammatory and antioxidant activities of borage flower extracts in macrophage assays.
32.  Comprehensive Review: Compiled directly in Ibrahim & Alshammaa (2023) (Section on anti-inflammatory effects). 27
33.  Barre, D. E. (2001). Potential of evening primrose, borage, black currant, and fungal oils in human health. Annals of Nutrition and Metabolism, 45 (2), 47–57. https://doi.org/10.1159/000046706
34.  Kernoff, P. B., Willis, A. L., Stone, K. J., Davies, J. A., & McNicol, G. P. (1977). Antithrombotic potential of dihomo-gamma-linolenic acid in man. British Medical Journal, 2 (6100), 1441–1444. https://doi.org/10.1136/bmj.2.6100.1441
35.  Fan, Y. Y., & Chapkin, R. S. (1998). Importance of dietary $\gamma$-linolenic acid in human health and nutrition. The Journal of Nutrition, 128 (9), 1411–1414. https://doi.org/10.1093/jn/128.9.1411
36.  De Caterina, R., Giannessi, D., Mazzone, A., Bernini, W., Lazzerini, G., Maffei, S., ... & Weksler, B. B. (1990). Incorporation of dihomo-$\gamma$-linolenic acid in human platelets and its effect on platelet function: A comparison of dietary vegetable oil sources. Prostaglandins, Leukotrienes and Essential Fatty Acids, 39 (4), 273–280.
37.  Engler, M. M. (1993). Comparative study of evening primrose oil and borage oil on vascular and platelet reactivity in hypertensive models. Lipids, 28 (8), 701–706.
38.  Ibrahim, R. M., & Alshammaa, D. A. S. (2023). Pharmacological aspects of Borago officinalis (Borage): A review article. Iraqi Journal of Pharmaceutical Sciences, 32 (1), 1–13. https://doi.org/10.31351/vol32iss1pp1-13
39.  Chares, J. M., et al. (1984). Effects of dietary gamma-linolenate supplementation on serum lipids and platelet function in insulin-dependent diabetic patients. The American Journal of Clinical Nutrition, 40 (2), 208–213.
40.  Das, U. N. (2007). Essential fatty acids and their metabolites in the pathobiology of diabetes mellitus and its complications. Biomarkers in Medicine, 1 (3), 441–458. https://doi.org/10.2217/17520363.1.3.441
41.  Cameron, N. E., & Cotter, M. A. (1997). Metabolic and vascular factors in the pathogenesis of diabetic neuropathy: Therapeutic opportunities with antioxidant and gamma-linolenic acid treatments. Diabetic Medicine, 14 (Suppl 4), S19–S23.
42.  Lu et al. (2007).  Secondary Review: Sovilj et al. (2010).
43. Lu et al. (20073)
44. Lu et al. (2007).
45. Wretensjö, Svensson, & Christie (1990).
46. Mhamdi et al. (2009)
47. : Mhamdi et al. (2009).
48. Bin Nayeem et al. (2017) (Phytoconstituents and pharmacological activity of Gauzaban (Borago officinalis Linn.): A review), as well as Ibrahim & Alshammaa (2023) and Kumari et al. (2023).
49. Ahmad et al. (2010) and classical monographs compiled in Bin Nayeem et al. (2017).
50. Asadi-Samani et al. (2014) and Kumari et al. (2023).
51. Concluding remarks from Bin Nayeem et al. (2017) and Kumari et al. (2023).
52. Gilani, A. H., Bashir, S., & Khan, A. (2007). Pharmacological basis for the use of Borago officinalis in gastrointestinal, respiratory and cardiovascular disorders. Journal of Ethnopharmacology, 114 (3), 511-519. https://doi.org/10.1016/j.jep.2007.08.032 Cited by: 181
53. Sayyah, M., Boostani, H., Pakseresht, S., & Malaieri, A. (2006). A broad spectrum of neuropsychopharmacological actions of Echium amoenum (Iranian borage/Gaozaban). Journal of Ethnopharmacology, 103 (3), 378–382. https://doi.org/10.1016/j.jep.2005.08.016