A Comprehensive Review on Applicability and Bioactivity of Rogan-I-Kunjad (Sesamum indicum L-Oil): Unani Prospective

Taxonomy of Kunjad (Sesamum indicum L.)

Kingdom: Plantae—(plant), Subkingdom: Tracheobionta(vascular plants), Superdivision: Spermatophyta—(seed plants), division: Magnoliophyta—(flowering plants), Class: Magnoliopsida—(dicotyledons), Subclass: Asteridae, Order: Scrophulariales, Family: Pedaliaceae—Sesame, Genus: Sesamum, Species: S. indicum L.¹¹

Habitat and Distribution of Kunjad (Sesamum indicum L.)

The suitable soil for satisfactory production of sesame is on soils with a pH range of 5.4 to 6.7 but is seriously affected by pH below this critical range. These, however, do not tolerate heavily salted or waterlogged soils well. Ninety to one-hundred twenty frost-free days are required for commercial sesame production. Over 23°C (73°F) warm conditions are favorable for growth and yields.¹² It is cultivated all over the world and in India it is widely distributed in Assam, Bihar, Gujarat, Uttar Pradesh, Madhya Pradesh, and Rajasthan.¹³

Morphology of Seeds of Sesamum indicum L

Characteristics of Rogan-I-Kunjad (Sesamum indicum L.)

As per the Unani classical text, sesame oil of the Indian verity is pale yellow to golden in color, while some of its verities are also dark yellowish in color. The oil which is extracted from Gair Mukasher (with covering) and Gair Birya Kunjad (without roasted) is known as Dahn-ul-Heel and its color is dark brownish, having a different flavor with mucilaginous, more stickiness, and the oil that is derived from Gair Mukasher (with covering), and Birya Kunjad (roasted seeds) is light pale yellow in color with less stickiness.^9,11 According to a study, the amount of lignans, tocopherols, and sterols in the oil produced from roasted sesame seeds was much lower than that of unroasted sesame seeds. The extracted oil's oxidative stability, and antiradical activity were all increased by roasting. In seeds oil roasted at high temperatures, a modest increase in Trans Fatty Acids (TFA) as well as triglyceride and diglyceride dimers was noted. For obtaining highly nutritious grade oil within the allowable range, 210 °C was the ideal roasting temperature. Utilizing this roasted sesame oil seed in plant-based diets may result in improved nutritional quality due to the great antioxidative efficacy of roasted seed oil.^8,16 Refined sesame seeds have more oxidative stability than unrefined sesame seeds oil due to more saturated fatty acids (SFA) and less Mono Unsaturated Fatty Acid (MUFA) and Polyunsaturate Fatty Acid (PUFA). The TOTOX value of refined sesame oil was significantly lower than unrefined. Oil processing was introduced as an effective way to reduce heavy metals.¹⁷ The temperament of the sesame oil is Har (hot) and Ratab (moist) in second grade and it is liquid at standard room temperature (37 °C).^9,10,18,19 As mentioned in classical Unani literature called “Muhit-i-Azam” by renowned Unani philosopher “Hakim Azam Khan,” the oil derived from the white luster surface seeds of sesame is the best form of sesame oil.⁹ Much research has been done on its genotypic verities with their significant characteristics. The comparison of the quality of oil derived from different types of sesame seeds showed that oil from white-colored seeds is the best in terms of its oil-yielding capacity, protein, PUFA, and MUFA. This indicates that light-colored seeds that are white and tan are superior in their quality and good for consumption as well as medicinal use²⁰ (►Table 2). Its life span is 2 years for its best use because it is prone to decomposing its phytochemicals and starting to oxidize and become rancid.²¹

Composition of Rogan-I-Kunjad (Sesamum indicum L.)

Sesame seed oil is rich in polyunsaturated fatty acids that is (43.62%) monounsaturated fatty acids (41.53%) and only (14.85%) SFA natural antioxidants, lignans like sesamin 0.07–0.61%, sesamolin 0.2–0.48%, sesaminol, sesamol, pinoresinol), (►Fig. 1) sterols (16–40%), and tocopherol derivatives (10–12%) claiming that oils with this quality are suitable for consumption.^1,8,22 The sesame oil extracted from white and black varieties of seeds contains 14.90% and 14.70% carbohydrates, respectively.²³ Its seeds are a rich source of protein (18–40%).²⁴ These bioactive components improve sesame oil's stability and shelf life, as well as provide several health advantages (►Table 3).

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Fig. 1

Lignans of Rogan-I-Kunjad (sesame oil).

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Uses of Rogan-I-Kunjad as per Unani System of Medicine

According to the Unani system of medicine, this oil has a hot and dry temperament, which is very much favorable for the person of Sawdāwī-al-Mizāj (Malencolic temperament—A type of temperament caused by the predominance of Sawda' (black bile) in the body, which is cold and dry; individuals with this type of temperament have thin built with prominent veins, blackish skin—Standard Unani Medical Terminology [SUMT]-UMI-0161, WHO International Standard Terminology on Unani Medicine [IUMT]-3.1.176).⁹ This oil is widely used as a medicine in the Unani system of medicine for the management of many diseases like Iltihāb (inflammation—(SUMT)-UMI-2358), Surfa Yabsiyya (dry cough—[SUMT]-UMA-0311, National Unani Morbidity Code [NUMC]-D-7.6, International Classification of Diseases [ICD-10]-R.05), Dīq-un-nafas (asthma[SUMT]-UMA-0247, [NUMC]-D-4, [ICD-10]-J-45), Sudda (obstruction—[SUMT]-UNI-0484), Waja' al-Mafāṣil (arthritis [NUMC]-L-4), Ḥudār [rheumatism [NUMC]-L-3), Dā' al-Tha'laboratory (alopecia areata [NUMC]-J-16), Ṣudā' (cephalgia/headache [NUMC]-A-36), Shūṣa (pleurodynia [NUMC]-D-11), Ramad Sawdāwī (melancholic conjunctivitis [NUMC]-B-1.4), Qīḥ al-Ṣadr (Empyema thoracis [NUMC]-D-26), Qishr al-Ra's (seborrheic dermatitis [NUMC]-J-15) Saraṭan (carcinoma [NUMC]-M-17] as well as all types of Qurūh (ulcer—[SUMT]-UMA-0200) as its properties are described in Unani medicine as a Muliyyan (laxative), Muḥallil (resolvent—[SUMT]-UMI-1910), Mufattiḥ (obstruent—[SUMT]-UMI-1942), Mufattiḥ-i-urūq (vasodilator—[SUMT]-UMI-0753), Muḥallil-i-waram (anti-inflammatory), Mundamil-i-qurūh (cicatrizing), Mualid-e-mani (spermatogenic[SUMT]-UMI-1937),^24,25,26 Hikka (pruritis—[SUMT]-UMI-1162, [NUMC]-J-57, [ICD-10]-L29-L29.9).^{6,7,16,19,25,26,27,28,29}

Rogan-I-Kunjad compound compositions have long been employed in Unani medicine. Here, some of the compound compositions that are most frequently utilized were discussed. In case of alopecia areata, seborrheic dermatitis, or dandruff, a mixture of Rogan-I-Kunjad and Barg-I Murad (leaf of Myrtus communis L.) is applied over the scalp. Rogan-I-Kunjad with Aspaghol (Plantago ovata) is used as a liniment in xerosis, burn, and ulcer. Rogan-I-Kunjad in the form of Qairooti (Cerate or salve) is used for cosmetic purposes. Eye ointment made up of Rogan-I-Kunjad with egg white is intended to treat conjunctivitis and other inflammatory condition of the eye. Preparation in the form of ear drop made up of Rogan-I-Kunjad with Filfil safaid (Piper nigrum L.) and Mastagi (Pistacia lentiscus L.) is used for otalgia and ear obstruction. Rogan-I-Kunjad with Munaqqa (Vitis vinifera L.) is used in Ḥikka (pruritus) and a solution of Rogan-I-Kunjad with Rogan-I gul (rose oil) in Ṣudā' (headache) is used as an oral administration.^9,18 Some of the marketed compound formulations of Rogan-I-Kunjad are mentioned in ►Table 4.

Phytochemicals in Rogan-I-Kunjad (Sesamum indicum L.)

There have been various types of phytochemicals isolated from seeds, seed oil, and other parts of the sesame plant, including polyphenols (whole plant), Phytate 5.18%, oxalic acid 2.2%, tannins 5.26mg/100 g, sterols (seeds), phenols (seeds), naphthoquinones (roots), anthraquinones (roots), triterpenes (seeds), cerebroside (flower), fatty acids (seeds), vitamins (seeds), essential amino acids (seeds, leaf, stems, flower), carbohydrates (seeds), and other organic compounds.² (►Table 3) However, higher amounts of sesamin (2.45 mg/g seed) and sesamolin (1.10 mg/g seed) were observed for Indian sesame species when compared with 65 sesame seeds harvested in Texas, United States (1.63 mg/g seed for sesamin and 1.01 mg/g seed for sesamolin).³⁰

Pharmacological Activities of Rogan-I-Kunjad (Sesamum indicum L.)

Antinociceptive Effect

In the Unani system, sesame oil has Muskin-I Alam (analgesic) and Muhalil-I warm (anti-inflammatory) properties and is used for the treatment of pain.^9,10 In an animal model of pain induced by acetic acid and formalin-induced writhing response, tail immersion, and hot plate latency test. It was shown that sesame oil caused significant reduction in abdominal writhes and sesamin inhibited biphasic paw licking response as compared with morphine. In the hot plate, latency time was increased after 60-minute administration of the drug³¹ (►Fig. 2).

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Fig. 2

Pharmacological target for Rogan-I-Kunjad (sesame oil).

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Pulmonary Diseases and Sesame Oil

In a study on an animal model of allergic asthma, ovalbumin (10 mg intraperitoneal) induced pulmonary edema and inflammation in female BALB/c mice, sesame oil showed a significant reduction in lung weight (wet-to-dry) as a result of improvement in pulmonary edema and significant decreases in proinflammatory cytokines (IL)-1β and IL-6, as well as total cell count and neutrophils; biomarkers like nitric oxide, inducible nitric oxide synthase, and immunoglobulin E (IgE) were also downregulated. This showed that sesame oil has the potential in treating allergic asthma.³⁵ Another preclinical study on an allergic asthma model treated with lignan of sesame oil called sesamin showed a significant decrease in cytokines of T-helper cell-2 (IL-4, IL-5, IL-13) and increase in interferon-gamma, and inhibited the production of IgE as well as decreased NF-κB P65 level by blocking the phosphorylation of IκB-α and P38 MAPK pathways³⁶ (►Fig. 2).

Cardiovascular Diseases and Sesame Oil

Sesame oil (5%) significantly reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apo A, serum glutamate pyruvate transaminase (SGPT), and serum glutamic oxaloacetic transaminase (SGOT) in comparison to the hypercholesteremic diet (1% cholesterol) in the rat model.³⁷

A randomized, triple-blind, crossover clinical study was conducted to demonstrate the effect of sesame oil on the APOA-1 gene in adults with and without type 2 diabetes mellitus. The result showed no significant differences in TC, triglycerides, LDL-C, HDL-C, apo A, apo B, or lipoprotein (a); however, significant differences were observed in LDL:HDL and TC:HDL ratios, blood pressure, as well as cardiovascular risk scores.³⁸ A study was conducted on a hypertensive animal model induced with cardiac hypertrophy using an injection of deoxycorticosterone and 1% sodium chloride. Sesame oil showed significant reduction in the size of cardiomyocytes, cardiac renin, angiotensin-converting enzyme, and angiotensin- II, and downregulated the expression of angiotensin receptor type-1, p38 MAPK, and JNK.³⁹ In a two-phase clinical trial, the first phase (acute phase) involved 30 hypertensive participants who consumed 35 g of sesame oil and were given corn or olive oil as a comparison. After 15 minutes, the objective parameters were observed, and the second phase (chronic phase) involved 60 days of treatment before the participants were evaluated. The study showed significant improvement in flow-mediated dilatation, and a significant decrease in intracellular adhesion molecule was observed after 60 days of treatment.⁴⁰ An antithrombotic activity was examined in animals by inducing thrombus using He–Ne laser; the sesame seeds significantly inhibited thrombosis in mice^41,42 (►Fig. 2).

Hepatic Diseases and Sesame Oil

In a study on C57BL/6J mice, a steatohepatitis animal model, sesame oil showed a significant reduction in hepatic fatty acid and cholesterol synthesis by downregulating both sterol element binding proteins (SREBPs)—SREBP-1 responsible for the synthesis of FAS enzyme and SREBP-2 responsible for synthesis of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase)—and increased fatty acid oxidation by upregulating Peroxisome Proliferator Activated Receptor Alpha (PPAR-α) expression responsible for synthesis of CTP-1. Endoplasmic reticulum (ER), stress and apoptosis maskers like glucose-regulated protein-78, protein kinase like endoplasmic reticulum kinase, phosphorylated eukaryotic initiation factor-2α, and X-box-binding protein-1 were significantly reduced; these markers showed there was significant improvement in ER stress, and apoptosis biomarkers like BAX, caspase-3, caspase-9, and C/EBP homologous proteins were also reduced.⁴³ On an animal model another study on nutritional fibrosing steatohepatitis was conducted, and it was found that there was a significant decrease in the degree of steatosis, activity of matrix metalloproteinase-2, 9 (MMP-2, 9), α-SMA expression, fibrotic collagen, SGPT, SGOT, and upregulated PPAR-γ expression.^44,45 (►Fig. 2).

Carcinoma and Sesame Oil

A preclinical study was conducted on C57BL/J6 mice, in which the mice survived that received whole-body γ-radiation with sesame oil compared with the control group due to the ability of sesame oil to diminish MN frequency in nucleated bone marrow cells and eliminate apoptotic cells. This study also demonstrated significant improvement in B-cell (CD 19) and T-cell (CD 4 and CD 8), decrease in TBARS, and significant enhancement in splenocytes proliferation in pretreated sesame oil mice.⁴⁶ An in-vitro study was conducted on human head and neck squamous cell carcinoma, that is, HSC-3 (tongue cell line), FaDu (pharynx cell line), and Ca9–22 (Gingiva cell line) to understand the anticancer and anti-metastatic effect of sesamin. This study showed there was a marked reduction in cell mortality, invasion, and migration in all cell lines at 40 µM of sesamin. There was downregulation of MMP-2 expression in HSC-3 and FaDu by 23 and 19%, respectively, and also downregulation of P-p38 and pJNK1/2 expressions leading to inhibition of MAPK pathway. It indicates that sesamin inhibits the synchronized movement of the tumor cell population.⁴⁷ In an in vitro study on colon cell lines, Human Colorectal Adenocarcinoma Cell Line (HT-29) and Human Colon Cancer Cell Line (HCT-111) demonstrated that ethanolic extract of Sesamum indicum L (ESL) significantly enhanced the radical scavenging activity and decreased cell growth in HT-29 and HCT-116 cells, respectively. The same study revealed a 3.2-fold increased population in sub-G1, G1/M by 2.3–6.6 population and reduction in G0/G1 and S phase of cell cycle as compared with control, which indicates that ESL significantly arrests cell cycle at G2/M.⁴⁸ An in vitro study was conducted on a lung adenoma cancer cell line to demonstrate the anticancer effect of sesame oil which showed that there was marked decrease in cell viability and enhancement in apoptotic activity by upregulation of Bax, PARP, TRAIL-R1, and TRAIL-R2 and downregulation of Bcl-2 expression.⁴⁹ An in vivo study was conducted to demonstrate the anticarcinogenic effect of sesame oil on serous papillary ovarian carcinoma. The result of this study indicated that there was a significant reduction in the size of the tumor, as well as downregulation of many metabolic enzymes responsible for cellular metabolism and growth and singling pathways like hypoxia inducible factor-1, ER pathways, and proteoglycans.⁵⁰ Another study on adult UChB, an experimental model of ovarian cancer, showed the anticancer effect of melatonin, while the result showed there were significant increases in plasma melatonin and downregulation of Her-2, p38 MARK, and p-AKT expression⁵¹ (►Fig. 2).

Male Sexual Health and Sesame Oil

An animal study was conducted on streptozotocin-induced diabetic rats to demonstrate the effect of sesame on testicular structure and male reproductive parameters. Sesame oil showed a significant improvement in histopathological changes and prevented testicular atrophy as compared with diabetic control; also, there were significant increases in male reproductive parameters, i.e., follicular stimulating hormone, testosterone, and luteinizing hormone, and decreases in serum glucose level in sesame-treated group as compared with control group.⁵² Male Sprague Dawley rats were used in an animal study to show the impact of melatonin on epididymis and sperm characteristics after exposure to fructose and bisphenol A. This study showed marked improvement in epididymis morphology, enhancement of sperm motility, and reduction in apoptotic sperm cells in the 20 mg/kg melatonin-treated group as compared with the fructose and bisphenol A group.⁵³ Another animal study was conducted on cyclophosphamide-induced spermatogenic dysfunction in which sesamin showed significant increases in the weight of testis, sperm concentration and motility, Johnsen's score, RNF8 expression, ub-H2A, and ub-H2B, and reverse morphological damage of sperm as well as testicular tissue derangement, significantly lowering the H2A and H2B⁵⁴ (►Fig. 2).

Arthritis and Sesame Oil

In an animal model of osteoarthritis, sesame oil significantly reduced muscular oxidative stress by decreasing LPO and ROS, and increased GSH level, GPx, and Nrf-2 expression after 7 days of administration.⁵⁵ A randomized, double-blind, clinical trial on knee arthritis was conducted to find out the effect of topical application of sesame oil, in which the result showed significant improvement in participants' walking speed, knee flexion angle, VAS, and WOMAC, after 4 weeks of intervention; this result suggested that sesame oil has a significant effect on OA.⁵⁶ The effect of sesame seed extracts on Freund's complete adjuvant-induced rheumatoid arthritis model showed that sesame oil markedly reduced paw volume, body temperature, IL-6, TNF-α, and ESR, and significantly upsurges spontaneous activity, body weight, hemoglobin, and RBC⁵⁷ (►Fig. 2).