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*Corresponding Author: Muhammad Arshad Ullah, Pakistan Agricultural Research Council, Islamabad, Pakistan.
Citation: Muhammad A. Ullah, Ali Hassan, Ameer Hamza. (2024), A Rare Syndrome with Tubulointerstitial Nephritis: TINU Syndrome, J. General Medicine and Clinical Practice, 7(2); DOI:10.31579/2639-4162/123
Copyright: © 2024, Muhammad Arshad Ullah. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 07 November 2023 | Accepted: 24 January 2024 | Published: 04 February 2024
Keywords: bronchodilation; theophylline; atherogenic index; antilithiatic; antihyperlipidemic
Ajwain seed analysis has revealed it to contain fiber (11.9%), carbohydrates (38.6%), tannins, glycosides, moisture (8.9%), protein (15.4%), fat (18.1%), saponins, flavone and mineral matter (7.1%) containing calcium, phosphorous, iron and nicotinic acid. Ajwain fruits yield 2% to 4% brownish essential oil, with thymol as the major constituent (35% to 60%). The non-thymol fraction (thymine) contains para-cymene, γ-terpenine, α- and β-pinenes, diketene, α-terpinene, and carvacrol. Minute amounts of camphene, myrcene, and α-3-carene also have been found in the plant. Alcoholic extracts contain a highly hygroscopic saponin. From the fruits, a yellow, crystalline flavone and a steroid-like substance has been isolated and it also contains 6-O-β-glucopyranosyloxythymol, glucoside and yields 25% oleoresin containing 12% volatile oil (thymol, γ-terpinene, para-cymene, and α- and β-pinene). The principal oil constituents of T. Ammi are carvone (46%), limonene (38%), and dillapiole (9%).
Ajwain is administered for curing stomach disorders, a paste of crushed fruits is applied externally for relieving colic pains; and a hot and dry fomentation of the fruits is applied on chest for asthma. Therapeutic uses of T. Ammi fruits include; stomachic, carminative and expectorant, antiseptic and amoebiasis, antimicrobial. Seeds soaked in lemon juice with P runs Amygdalus (badan) are given in curing amenorrhea and it is also used as antipyretic, febrifugal and in the treatment of typhoid fever.
The antihypertensive effect of T. Ammi administered intravenously in vivo, and the antispasmodic and bronchodilation actions in vitro showed that calcium channel blockade has been found to mediate the spasmolytic effects of plant materials and it is being considered that this mechanism contributed to their observed result and supported the traditional use of T. Ammi in hyperactive disease states of the gut such as colic and diarrhea as well as in hypertension. Ajwain seeds revealed significant reduction of cough number which may be a result of its potent antitussive effect. The bronchodilator effect of decocted extract of Ajwain on the asthmatic patients’ airways was examined in a subsequent trial study. According to the results, the extract has a relatively bronchodilator effect on asthmatic airways compared to the effect of Theophylline at concentrations used.
Ajwain was attributed to have diuretic and antilithiatic activity in ethnopharmacological reports. Accordingly, a human study was performed and in which, seeds of Ajwain were decocted in milk and given orally to volunteers suffering from urinary stone for a nine days period. The results were reported satisfactory against pure ca-oxalate stone. Another activity which has been proved for Ajwain is the antihyperlipidemic property. An in vivo study revealed that Ajwain seeds powder is extensively effective on lipid profile and can decrease total cholesterol, LDL-cholesterol, triglycerides and total lipids. Moreover, organic extract of seeds reduced atherogenic index and increased the level of HDL-cholesterol in albino rabbits.
Ajwain was evaluated for the potentiality of antihypertensive and antispasmodic activity. In the related investigation, the aqueous-methanolic extract of the seeds caused a dose dependent decrease in arterial blood pressure in anaesthetized animal models. Furthermore, inhibitory effect on the K+-induced contractions was seen in isolated rabbit aorta and jejunum preparations during the application of Ajwain extract. These findings prove the potential antihypertensive and antispasmodic activity of Ajwain.
A number of chemical constituents have been reported for the herb. Fiber (11.9%), carbohydrates (24.6%), tannins, glycosides, moisture (8.9%), protein (17.1%), fat (21.1%), saponins, flavones and other components (7.1%) involving calcium, phosphorous, iron, cobalt, copper, iodine, manganese, thiamine, riboflavin and nicotinic acid are of reported phytochemical constituents of Ajwain (Ranjan et al., 2012; Qureshi and Kumar, 2010). In the alcoholic extraction process, a large amount of saponin has been derived (Ranjan et al., 2012). Similar to the most species of the family Pinaceae, Ajwain is famous for its brownish essential oil. Apparently, presence of an Ajowan essential oil is responsible for its odor and taste. Hence fruits of Ajwain accumulate up to 5% essential oil in its compartments (Minima and Toppi, 2002).
However, some investigation reported the yield of fruits essential oil up to 9% which may be considerable. Usually, Thymol is the main Ajwain essential oil constituent and may be yielded from 35% to 60% (Ishikawa et al., 2001; Starshinas et al., 2014).
The non-thymol fraction (Thymine) contains Para-cymene, Gamma-terpinene, Alpha-pinene, Beta-pinene, α-terpinene, Styrene, Delta-3-carene, Beta-phellandrene, terpinene-4-ol and Carvacrol (Ranjan et al., 2012; Mohagheghzadeh et al., 2005). On the other hand, in an investigation, carvone (46.2%), limonene (38.1%) and dillapiole (8.9%) were introduced as principal oil constituents. Also oleic, linoleic, palmitic, Petroselinum acid, resin acids are isolated from fruits of Ajwain (Qureshi and Kumar, 2010). New glycosyl constituents such as 6-hydroxycarvacrol2-O-β-D-Glucopyranosideand3,5-Dihydroxytoluene3-O-β-DGalactopyranoside are recently reported from fruits of Ajwain.
In order to evaluate the analgesic and antinociceptive activity of Ajwain, an In vivo investigation was carried out using a Tail-flick Analgesia meter Device (Dashti-Rahmat Abadi et al., 2007). The study revealed that the ethanolic extract significantly increase in Tail-Flick Latency (TFL) within 2 hours post-drug administration. An experimental trial study has also been carried out to compare the antinociceptive effect of the hydroalcoholic extract of Ajwain with morphine sulphate using formalin test. Findings revealed that Ajwain extract exhibited antinociceptive effect on both early and late phases (Hejazi an et al., 2008). Similar study has been done on the Ajwain total essential oil which was significantly effective on the late phase of formalin test (Hejazi an, 2006) and it may be due to the presence of thymol in essential oil. In addition, under a randomized controlled placebo control clinical trial, the herb essential oil was assayed for the analgesic effect in neuropathic feet burn. Results revealed that Ajwain essential oil significantly reduced the feet burn compared to placebo (Petr amfAR et al., 2013). To assay the antibacterial efficacy of Ajwain, acetone and aqueous extracts were tested against Enterococcus faecalis, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Salmonella typhi, Salmonella typhi- curium, Shigella flexneri, and Staphylococcus aureus using agar diffusion assay (Kaur and Arora, 2008). The study showed that acetone extract shows more activity compared to the aqueous extract. In another study, ethanolic extract of Ajwain possessed antibacterial activity against eight strains of Helicobacter pylori (Zaidi et al., 2009). Also, methanolic extract of Ajwain exhibited bactericidal activity against 11 species at 2mg/well in agar well-diffusion method. It was measured by Diameter of Inhibition Zones (DIZ). DIZ was over 15mm against Staphylococcus aureus and Staphylococcus epidermidis; 10–14 mm against Pseudomonas aeruginosa and Bacillus poilus; 7–9 mm against Escherichia coli, Klebsiella pneumonia as well as Bordetella bronchiectasis. On the other hand, no activity was reported against Pseudomonas fluorescens and Micrococcus luteus (Shahidi, 2004).
It is reported that the essential oil extracted from the seeds of Ajwain can exhibit insecticidal activity in the oviposition step as well as egg hatching and developmental inhibitory activities against Clonorchis chinensis (Chaubey,2008; Chossudovsky et al., 2002). A bioassay-guided fractionation was prepared by introducing the crude extract to flash chromatography. HPLC analysis was done for both crude extract and active fraction (Mathew et al., 2008). Anthelmintic activity of Ajwain was carried out by considering the Haemanthus contorts in sheep and Ascaris lumbricids humans. Results were due to loss of energy reserves by interference with the energy metabolism of parasites through potentiating the ATPase activity. Ajwain has also been reported to exhibit cholinergic activity with peristaltic movements of gut. Hence this fact may help in expulsion of intestinal parasites and be a contributory factor to its anthelmintic activity (Tamura and Iwamoto, 2004; Jabbar et al., 2006).
Ajwain was also evaluated for its nematocidal activity. A survey was done on the total essential oil components of Ajwain that showed significant nematocidal activity against pinewood nematode, Bursaphelenchus xylo-pilus. Nematocidal activity of Ajwain essential oils LC50values was measured as 0.431mg/ml (Park et al., 2007) and it was mainly attributed to the activity of Thymol and Carvacrol.
Ajwain was also evaluated for exhibiting anti–inflammatory effect. Accordingly, both total alcoholic extract and total aqueous extract possess in vivo significant anti–inflammatory effect (Thangam and Dhananjayan, 2005).
Ajwain seeds revealed significant reduction of cough number which may be a result of its potent antitussive effect (Bozcaada and Shaikh, 2000). Relative studies showed the inhibitory effect of both Ajwain extract and essential oil on Histamine (H1) receptors of isolated guinea-pig tracheal chains (Bozcaada and Shaikh, 2000). In another study, in the field of respiratory, bronchodilator effects of different fractions of Ajwain essential were examined. Results showed that the relaxant and bronchodilator effect of essential oil fractions may be due to the amount of Carvacrol (Bozcaada et al., 2003).
The bronchodilator effect of decocted extract of Ajwain on the asthmatic patients’ airways was examined in a subsequent trial study. According to the results, the extract has a relatively bronchodilator effect on asthmatic airways compared to the effect of Theophylline at concentrations used (Bozcaada et al., 2007).
Ajwain was attributed to have diuretic and anti-lithiasis activity in ethnopharmacological reports. Accordingly, a human study was performed and in which, seeds of Ajwain were decocted in milk and given orally to volunteers suffering from urinary stone for a nine days period. The results were reported satisfactory against pure ca-oxalate stone (Sabar, 2010).
Another activity which has been proved for Ajwain is the antihyperlipidemic property. An in vivo study revealed that Ajwain seeds powder is extensively effective on lipid profile and can decrease total cholesterol, LDL-cholesterol, triglycerides and total lipids. Moreover, organic extract of seeds reduced atherogenic index and increased the level of HDL-cholesterol in albino rabbits (Javed et al., 2006).
Detoxification of aflatoxins by seed extract of Ajwain can support the related traditional reports. Hence in an experimental study, Ajwain seed extract exhibited the maximum degradation of aflatoxin G1 (Elishama et al., 2010).
The antioxidant and ameliorative property of Ajwain extract has been evaluated on hexachlorocyclohexane induced oxidative stress and toxicity in an in vivo investigation. Accordingly, results revealed that the dietary Ajwain extract would reduce the toxicity resulted from hepatic free radical stress (Anila Kumar et al., 2008).
For the evaluation of Ajwain antiviral activity, an in vitro assay was carried out on the methanolic extract of the herb which showed significant inhibitory effects on Hepatitis C Virus (HCV) protease (Hussein et al., 2000).
The extract also possessed preventive effects against CCl4-induced prolongation of pentobarbital sleeping time as well as equilibrating the level of hepatic enzymes, Alkaline Phosphatase (ALP) and Aminotransferases (AST and ALT) during liver damage (Gilani et al., 2005). Using different ulcer models, Ajwain ethanolic extract resulted in significant ulcer index decrease in animal pre-treated with and also exhibited ulcer protection in all models. Overall, the extract reduced the ulcerative lesions compared to control group of animal model (Ramaswamy et al., 2010). Ajwain was evaluated for the potentiality of anthia- pretensive and antispasmodic activity. In the related investigation, the aqueous-methanolic extract of the seeds caused a dose dependent decrease in arterial blood pressure in anaesthetized animal models. Furthermore, inhibitory effect on the K+-induced contractions was seen in isolated rabbit aorta and jejunum preparations during the application of Ajwain extract.
Traditional practitioners recommended the herb as a digestive stimulant medicine. It is now proved that Ajwain can increase the secretion of gastric acid, bile acids and activity of digestive enzymes. It may also reduce the food transient time (Vasudevan et al., 2000; Platel and Srinivasan, 2001). As the enzyme modulatory activity, Ajwain reinforced the pancreatic lipase and amylase effectiveness, which may support the digestive stimulant activity (Ramakrishna et al., 2003).
C. copticum or Ajwain belongs to the Pinaceae plants family and its seeds are used extensively as a food additive in India and mainly therapeutically effective, with hot nature. C. capsicums an Egyptian aborigine plant. This plant grows in arid and semiarid fields in different regions of central Europe, Asia, India (most crops are in the states of Rajasthan, Gujarat, and West Bengal), Iran (especially eastern regions of\ Baluchistan), Iraq, Afghanistan, and Pakistan (Zahin et al., 2010).
In traditional medicine, different therapeutic applications for C. capsicum have been described and in Persian traditional medicine it is used for thousands of years. The bronchodilator, antitussive, and ant dyspnea effects were demonstrated for C. capsicum. The therapeutic effects of this plant in gastrointestinal disorders, such as reflux, cramps, abdominal tumors, abdominal pain, and Helicobacter pylori, as well as in eye infection disorders, have been demonstrated (Starshinas et al., 2013).
Therapeutic uses of C. capsicum seeds also include carminative, antiseptic, amoebiasis expectorant, antimicrobial, antiparasitic, antiplatelet-aggregatory, and antilithiatic as well as treating common cold and acute pharyngitis. Abortifacient, galactagogic, and diuretic activities have been observed for this plant (Chauhan et al., 2012; Ranjan, 2011). There is also anticarcinogenic potential evidence for C. capsicum (Lim, 2013). It has been shown that this plant has also fetotoxicity, abortion potential, and galactagogue properties (Jeet et al., 2012).
Different names of the plant in various languages (vernacular name) are Sanskrit: Yamini, Assamese language: Jain, English: Bishop’s weed, Hindi, Baluchi: Ajowan and Spica, Gujarati Language: Ammo, Canada: Oma, Malaysia: Oman, Arabic: Khella or khellin, Persian: nankhah, zenian, chlordane, and South Khorasan: ago (Brito-Arias, 2007).
The constituents of the seed of C. capsicum included carbohydrates (38.6%), fat (18.1%), protein (15.4%), fiber (11.9%), tannins, glycosides, moisture (8.9%), saponins, flavone, and mineral matter (7.1%) containing calcium, phosphorous, iron, cobalt, copper, iodine, manganese, thiamine, riboflavin, and nicotinic acid (Bairwa et al., 2012). C. capsicum grows indifferent areas of the world containing different compounds. Main components of the oil of Iranian and African C. capsicum oil are carvacrol, -terpinene, and p-cymene while thymol (97.9%) is the main component of south Indian plant oil. It was also reported that thymol (45.9%),
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