Aatrilal (Ammi majus L.), an important drug of Unani system of medicine: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Ammi majus L. (Aatrilal) a member of the family Apiaceae, is native to Egypt and widely distributed in Europe, the Mediterranean, and West Asia. It has been used for the treatment of various dermatological disorders particularly vitiligo in the Unani system of Medicine for ages. In traditional medicine, fruits are used as an emmenagogue as well as a diuretic, blood purifier and to treat leprosy, urinary and digestive disorders. AIM OF THE REVIEW: This paper aims to highlight the medicinal properties of Aatrilal in view of its temperament and phytoconstituents; to signify its potential in the treatment of vitiligo and other ailments as mentioned in Unani system of medicine and also to explore its phytochemistry, pharmacological and clinical studies. MATERIALS AND METHODS: Aatrilal was explored in classical Unani literature for its temperament (mizaj), medicinal properties and therapeutic uses. Published works available on PubMed, Science Direct, and Google Scholar were referred to collect all the available information regarding its phytochemicals and pharmacological studies. All relevant articles up to 2020 were referred including 15 classical Unani books, 15 English books, 72 research, and 3 review papers. The plant's scientific names were validated using 'The Plant List' (www.theplantlist.org). Standard Unani Medical Terminology published by Central Council for Research in Unani Medicine in collaboration with the World Health Organization was used to describe the appropriate Unani terminologies. Glossary of Indian Medicinal Plants and different indexed journals were consulted for botanical and English names. RESULTS: Aatrilal has been used in traditional medicine for ages. Due to controversies in its identity, it was adulterated and substituted with many drugs. The real identity of Aatrilal is now established as the fruit of A. majus L. Despite having numerous pharmacological activities, it is considered the first-line drug for the treatment of vitiligo. It is a rich source of furanocoumarins (xanthotoxin, also known as 8-methoxypsoralen, bergapten, imperatorin, isopimpinellin) with other compounds viz. flavonoids, terpenoids, proteins, essential oil constituents, etc. It has been reported for anti-inflammatory, analgesic, antibacterial, antiviral, cytotoxic, and many other activities. Clinical trials have shown the therapeutic potential in vitiligo and other skin disorders. CONCLUSION: Based on the available literature, it can be concluded that Aatrilal is a drug that has been effectively used in Unani system of medicine for centuries to treat the cases of vitiligo and other dermatological disorders. It has been studied extensively for its phytopharmacological properties. Raw extracts of A. majus form the crux of the main research. Many potentially bioactive compounds are included in the essential oil, but to our knowledge, no detailed studies of its biological activity are yet available. Therefore, our suggestion is to focus future research on essential oil and its ingredients.

Anti-inflammatory and analgesic activity of Habbe Gule Aakh, A polyherbal Unani formulation in animal models.

BACKGROUND: Habbe Gule Aakh is extensively used in Unani medicine for anti-inflammatory and analgesic activity. OBJECTIVE: To evaluate anti-inflammatory and analgesic effects of Habbe Gule Aakh on Wistar rats and Swiss mice of either sex. MATERIALS AND METHODS: The study was carried out in Wistar rats for anti-inflammatory activity while Swiss mice were used for analgesic activity. In both the tests animals were divided into five groups of six animals each which served as control, standard and test groups A, B and C. For anti-inflammatory activity, method reported by Amman was followed. For analgesic activity, Koster's protocol was adapted. RESULTS: Significant (P < 0.01) reduction in the paw volume was noted in all the test groups but less than the standard drug. Mean writhes of group B and C reduced significantly (P < 0.01) demonstrating analgesic effect. CONCLUSION: The study validated the claim of Unani medicine of use of Habbe Gule Aakh in inflammation and pain. Further, phytochemical studies are needed to know the exact mechanism of action of this formulation.

In vitro antilithiatic activity of the hydro-alcoholic extract of Cinnamomum zeylanicum Blume bark on calcium oxalate crystallization.

OBJECTIVE: The study examines the effect of the hydro-alcoholic extract of Cinnamomum zeylanicum Blume bark on crystallization of calcium oxalate. METHODS: The antilithiatic effect of various concentrations of the hydro-alcoholic extract of C. zeylanicum was investigated at various stages of stone formation, using Cystone as a standard reference drug. The effect on calcium oxalate crystallization was evaluated by measuring the change in turbidity over time, during crystal nucleation, growth and aggregation, in the metastable solution of calcium chloride and sodium oxalate. The slope from the change in turbidity over time was measured using a spectrophotometer at 620 and 214 nm in respective tests. The inhibition rate was estimated by comparing turbidity in the presence and absence of extract. Crystals formed under experimental conditions were observed under a light microscope, and number and shape of the crystals were assessed in a randomly selected field. Phytochemical analysis and high-performance thin-layer chromatography of the extract was also carried out. RESULTS: C. zeylanicum significantly reduced crystal nucleation at concentrations of 4, 8 and 10 mg/mL (P < 0.001). The inhibition percentage of crystal growth was between 28.30% and 92.46% in the presence of C. zeylanicum extract and from 20.76% to 64.15% with various concentrations of Cystone. The maximum inhibition of crystal growth was obtained from C. zeylanicum at 2 mg/mL (92.46%). Microscopic examination revealed a reduction in the number and size of crystals. In the aggregation assay, the inhibition percentage of C. zeylanicum was between 16.27% and 100%, while Cystone was from -214.68% to 100% at different concentrations. The highest (100%) inhibition of aggregation was found at 4 mg/mL of both the test and standard drugs. CONCLUSION: We found that C. zeylanicum hydro-alcoholic extract has notable inhibitory effects on various stages of crystallization, in terms of turbidity of solution, as well as the crystal size, number and morphology.

Approaches for preparation methods of Murakkab, an Unani formulation.

Murakkab drugs of Unani medicine have remained an important aspect of disease treatment since antiquity. Physicians prepared different formulations for various diseases. The formulations thus prepared have always been of two categories. One category of Murakkab drugs was those which were formulated empirically and remained in use without conceptual framework behind these formulations. These formulations were categorized as Mujarrab (tested) formulations. The other category of formulations was prepared in consideration with theoretical framework of Mizaj (temperament) and Usoole ilaj (treatment strategy) and then tested by physicians. This category forms a large chunk of formulations in the formulary sections of the literature of Unani medicine. Present paper explores various approaches for formulating Murakkab drugs of the second category keeping in view the actions of the ingredients of the drug formulation, and treatment strategy of the disease for which the formulation was prepared. It elucidates the approaches of formulating compound drug formulations with the logic of including various individual ingredients. The study exemplifies two compound formulations to illustrate the approaches used to formulate compound formulations of Unani medicine.

Effect of Piper cubeba L. fruit on ethylene glycol and ammonium chloride induced urolithiasis in male Sprague Dawley rats.

BACKGROUND: To investigate the antilithiatic effect of hydroalcoholic extract of Kabab Chini (Piper cubeba L.) fruit in male Sprague Dawley rats. METHODS: Rats were divided into six groups of six each. Group I received regular rat food and drinking water ad libitum. Groups II to VI were administered with ethylene glycol (EG) 0.75% (V/V) and ammonium chloride (AC) 1% (W/V) in drinking water for 7 days to induce urolithiasis. From 8th day Group I received 1 mL of 5% gum acacia. Group IV was treated with Cystone; V and VI groups with the hydro-alcoholic extract of Piper cubeba L. Treatment was continued for further 14 days, thereafter animals sacrificed. While Group II animals were sacrificed just after 7 days treatment with EG and AC. Group III was left untreated until 14 days and sacrificed on 22nd day. Crystalluria was analyzed on 8th and 22nd day while, urinary calcium, phosphorus, creatinine, sodium and magnesium on 22nd day. Biochemistry and histopathological studies of kidney were also carried out. RESULTS: Test groups showed significant reduction (p < 0.001) of crystals in urine. Serum creatinine and urea (p < 0.01) were also decreased significantly. Urine analysis showed significant increase in magnesium while calcium, sodium, chloride and phosphorus significantly decreased along with histopathological improvement in kidney tissue in treated groups. CONCLUSION: From the above results it can be concluded that hydroalcoholic extract of P. cubeba L. fruit has significant inhibitory effect in calcium oxalate urolithiasis.

Hajrul yahood (Lapis judaicus): An important mineral drug of Unani system of medicine for the management of urolithiasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Hajrul yahood (Lapis judaicus) is a mineral drug used in different dosage forms in Unani system of medicine and claimed to be effective in the management of urolithiasis. AIM OF THE STUDY: To explore the role of Hajrul yahood in the management of urolithiasis along with determination of its morphological, ethnomedicinal, physicochemical and pharmacological attributes. MATERIALS AND METHODS: A review of literature on Hajrul yahood was undertaken using the bibliographic database viz. Pub Med, Google Scholar, Science Direct and Scopus. The search was conducted using the terms 'Hajrul yahood', 'Lapis judaicus', 'Majoon Hajrul yahood' and 'Kushta Hajrul yahood'. Further books, monographs and reports on Lapis judaicus published in Urdu and English were used to compile the information. RESULTS: Hajrul yahood as such and as an ingredient in multidrug formulations has been used for the treatment of kidney and bladder stones since ancient times mainly by the practitioners of traditional medicines. Literature of Unani medicine clearly indicated that Hajrul yahood and its different formulations are safe and have antilithiatic effect. Sufficient information in respect of morphological, physicochemical and ethnomedicinal properties of Hajrul yahood are available but very few pharmacological and clinical studies have been conducted. The available reports on Hajrul yahood and its products mainly Cystone® though has shown varying results but on the whole indicated possible antilithiatic effect. The studies conducted so far have been limited by small patient numbers, weak methodology, and poor study design therefore a conclusive result cannot be arrived at. CONCLUSION: Hajrul yahood and its formulations have been claimed by Unani medicine to be useful in the management of urolithiasis. Some of the scientific reports also suggest the possibility of such an effect however further elaborate and comprehensive studies are required to validate such a claim.

Antilithiatic effect of Peucedanum grande C. B. Clarke in chemically induced urolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Duqu (Peucedanum grande C. B. Clarke) has been used by Unani physicians since ancient times in retention of urine, renal and bladder calculi, nephritis and other associated disorders in different dosage forms. AIM OF THE STUDY: The aim of the study was to evaluate the antiurolithiatic activity of Peucedanum grande C. B. Clarke in experimental model. MATERIALS AND METHODS: The experiment was carried out in male Sprague Dawley rats divided into 5 groups of 8 animals each. Animals of negative control received 1ml of 5% Gum acacia throughout the study. Remaining four groups received Ethylene glycol 0.75% and Ammonium chloride 1% by adding in their drinking water for first seven days to induce urolithiasis. From 8th day, positive control received 1ml of 5% Gum acacia, standard control received Cystone in the dose of 750mg/kg while test groups A and B were treated with hydroalcoholic extract of test drug in the dose of 56mg/kg and 97mg/kg respectively up to 21 days, thereafter the animals were sacrificed. Number of CaOx crystals in urine, levels of serum calcium, phosphorus, creatinine, urea, urinary calcium and sodium were observed. Kidney homogenate analysis and histopathology were also carried out. RESULTS: Test drug reduced number of CaOx crystals in urine (p<0.001); levels of serum calcium, phosphorus, creatinine, (p<0.001) urea, (p<0.05); urinary calcium (p<0.001) and sodium decreased significantly in standard and test groups. The urine volume increased significantly (p<0.05, 0.01) in both the test groups. Histopathology of kidney showed no CaOx crystal deposition in both the test groups. CONCLUSION: On the basis of above findings, it can be concluded that the test drug possesses significant antiurolithiatic activity.

Effect of combination of Withania somnifera Dunal and Tribulus terrestris Linn on letrozole induced polycystic ovarian syndrome in rats.

BACKGROUND: To investigate the effect of the combination of hydroalcoholic extract of Withania somnifera (WS) and Tribulus terrestris (TT) on letrozole induced polycystic ovarian syndrome (PCOS) in rat. METHODS: Twenty four female Wistar rats of regular estrus cycle were divided into four groups of six animals each. The negative control group received 1 mL of 0.5% carboxy methyl cellulose. The animals of the other groups were treated with letrozole (1 mg/kg) for 21 days for induction of PCOS. The animals of the positive control group were sacrificed on the 22nd day. In the test and standard groups, the treatment was started from the 22nd day and continued for a further 28 days. The test group was treated with hydroalcoholic extract of the combination of WS and TT (198 mg/kg) and the standard group with clomiphene citrate (1 mg/kg). Throughout the study, vaginal smears were collected daily from each animal for the determination of different phases of the estrus cycle. After completion of the treatment schedule all the animals of each group were sacrificed; analysis of hormones, total cholesterol, blood glucose, ovarian and uterine weight, and histopathological study of the ovary were carried out. RESULTS: The combination of the test drugs showed significant effects in normalizing the estrus cycle after being altered by letrozole. In the positive control group follicle-stimulating hormone level was decreased although luteinizing hormone, estradiole, and testosterone levels were increased (p < 0.05), however, after treatment the reverse effect was observed in the level of these hormones. Significant reduction in serum total cholesterol was also observed (p < 0.05). The test drugs decreased ovarian weight, and uterine weight was also returned to normalcy. Histopathology of the ovary showed almost normal ovary. CONCLUSION: The above findings indicate the effectiveness of the combination of hydroalcoholic extract of WS and TT against letrozole induced polycystic ovarian syndrome in rat. This validates the usefulness of combination in PCOS and other related disorders as mentioned by Unani physicians.

Homology modeling and assigned functional annotation of an uncharacterized antitoxin protein from Streptomyces xinghaiensis.

Streptomyces xinghaiensis is a Gram-positive, aerobic and non-motile bacterium. The bacterial genome is known. Therefore, it is of interest to study the uncharacterized proteins in the genome. An uncharacterized protein (gi|518540893|86 residues) in the genome was selected for a comprehensive computational sequence-structure-function analysis using available data and tools. Subcellular localization of the targeted protein with conserved residues and assigned secondary structures is documented. Sequence homology search against the protein data bank (PDB) and non-redundant GenBank proteins using BLASTp showed different homologous proteins with known antitoxin function. A homology model of the target protein was developed using a known template (PDB ID: 3CTO:A) with 62% sequence similarity in HHpred after assessment using programs PROCHECK and QMEAN6. The predicted active site using CASTp is analyzed for assigned anti-toxin function. This information finds specific utility in annotating the said uncharacterized protein in the bacterial genome.

Efficacy of Adiantum capillus veneris Linn in chemically induced urolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Adiantum capillus veneris Linn has been recommended in ancient literature of Unani system of medicine as an important ingredient of many formulations for the treatment of urolithiasis. Its decoction has long been used for the same purpose by several Unani physicians. AIM OF STUDY: To investigate the antiurolithiasic effect of the hydro alcoholic extract of Adiantum capillus veneris Linn in male Sprague Dawley rats. MATERIAL AND METHODS: The effects of oral administration of hydro alcoholic extract of test drug were studied on calcium oxalate urolithiasis. A total of 48 rats were used for the study. The animals were divided into six groups of eight animals each. Plain control rats were treated with distilled water only, throughout the study period, whereas in other groups nephrolithiasis was induced by providing drinking water containing 0.75% ethylene glycol and 1% ammonium chloride for 7 days. Thereafter, urine was examined for the presence of crystals. Negative control group A rats were sacrificed after 7 days, whereas negative control group B was left untreated up to the end of study. Test groups were treated with 127.6 mg/kg and 255.2 mg/kg of test drug and standard control with Cystone (750 mg/kg) for 21 days. At the end of experiment, number of crystals in urine and levels of calcium, phosphorus, urea and creatinine in serum were observed. Histopathological study of the kidney was done by light microscopy. RESULTS: Urine microscopy showed significant reduction (p<0.001 and p<0.01) in the number of crystals in test groups A and B respectively. Serum levels of calcium, phosphorous, and blood urea were found to be decreased significantly in all the groups. In both the test groups, serum creatinine level was found to be similar as in plain control. The animals treated with test drug showed much improvement in body weight. Histopathology of kidney showed almost normal kidney architecture in treated groups. CONCLUSION: The above findings indicate the antiurolithic activity of Adiantum capillus veneris Linn, and thus, validate the claims of Unani physicians for its medicinal use in urolithiasis.

Nephroprotective effect of Kabab chini (Piper cubeba) in gentamycin-induced nephrotoxicity.

Kabab chini (KC) (Piper cubeba) is an important drug in Unani Medicine, widely described to be effective in renal diseases, and physicians are using it as a protective and curative agent in various renal disorders from ancient times. The present study was designed to evaluate the nephroprotective effect of KC against gentamycin-induced nephrotoxicity in Wistar rats. This was studied in two different sets of tests, in which both the protective as well as the curative effects were evaluated in groups of albino rats. The powder of the test drug was administered orally in a dose of 810 mg/kg and 1220 mg/kg, in suspension form, in the pre- and post-treated models. The nephroprotective effect was assessed on the basis of biochemical estimation of serum urea and creatinine levels and histopathological examination of the treated kidney. The effect observed in the pre-treated and post-treated groups was compared with plain as well as negative control groups using one-way ANOVA with Dunnett's multiple pair comparison test. The findings of the two tests demonstrated that KC produced a significant nephroprotective effect in both pre-treated and post-treated groups. The results of our study indicate that KC possesses significant benefit against gentamycin-induced nephrotoxicity.