Pharmacological Screening of Substituted Benzimidazole Derivatives

In the present study some substituted benzimidazole derivatives were screened for several biological activities. The synthesized compounds were subjected to evaluation of central analgesic, anti-inflammatory, cytotoxicity, antimicrobial and antioxidant activities by radiant heat induced tail flicking, carrageenan induced rat paw edema inhibition, brine shrimp lethality bioassay, disc diffusion and DPPH free radical scavenging methods, respectively. Compounds 2a, 2c and 2d elongated the tail flicking time by 58.07-, 51.59- and 76.65%, respectively (p < 0.001) at 50 mg/kg body weight dose compared to the standard morphine (87.17%). Compounds 2b, 2c and 2d showed prominent anti-inflammatory activity at 100 mg/kg body weight dose (% of paw edema inhibition 81.75%, 79.09% and 86.69%, respectively) compared to the standard aceclofenac (87.83%). Among the synthesized benzimidazole derivatives, compounds 1a, 1b, 1c, 2a and 2d exhibited potent cytotoxicity with the IC50 values of 5.47-, 11.92-, 4.55-, 7.63- and 7.94 μg/ml, respectively. In addition, compounds 1c and 2d displayed mild to moderate zone of inhibition (8-12 mm). On the other hand, 1a and 1b showed very mild antioxidant activity with IC50 values of 12.25 × 103 μg/ml and 87.33 ×103 μg/ml. Among all the derivatives, 2c, 2d and 1c can be potential candidates for designing new analgesic, anti-inflammatory and anti-cancer agents in future. Dhaka Univ. J. Pharm. Sci. 20(1): 95-102, 2021 (June)

Effect of Gooseberry (Physalis angulata) Ethanol Extract in Wistar Rats Carrageenan-Induced Paw Oedema

Gooseberry is an herbaceous plant that contains flavonoids. Flavonoid is one of the secondary metabolites that have an anti-inflammatory effect. This study aims to determine the effect of using ethanol extract of gooseberry as an anti-inflammatory in carrageenan-induced paw edema. This study was in vivo experimental laboratory using a completely randomized design of 25 Wistar rats and divided into five groups. The negative control group was given carboxymethylcellulose. The positive control group has given diclofenac sodium 27 mg/200 gBW. The sample test group has given ethanol extract of gooseberry with 3.6 mg/200 gBW, 5.4 mg/200 gBW, and 7.2 mg/200 gBW dosage. Paw rat’s inflammation induced by injecting carrageenan and measured from 1st to 6th hour using a pletismometer. This study has conducted at Pharmacology Laboratory, Universitas Islam Bandung, and the Laboratory of Therapy and Pharmacology, Universitas Padjajaran, from June to September 2019. The result of average edema volume paw rats using the Kruskal-Wallis test on the 6th hour was p=0.02 (p<0.05). The Mann-Whitney test was p<0.05, showing differences between negative control and positive control and sample test groups. One-way ANOVA test on the percentage of edema inhibition between positive control and sample test group had p=0.107. It shows no significant difference. An effect of ethanol of extract of gooseberries as an anti-inflammatory with the highest percentage of edema inhibition is 5.4 mg/200 gBW dosage. The flavonoid content in gooseberries is thought to inhibit the formation of prostaglandins by inhibiting the cyclooxygenase enzyme. In conclusion, the ethanol extract of gooseberry can be anti-inflammatory. EFEK EKSTRAK ETANOL CIPLUKAN (PHYSALIS ANGULATA) TERHADAP EDEMA TELAPAK KAKI TIKUS GALUR WISTAR YANG DIINDUKSI KARAGENANCiplukan adalah tanaman herbal yang mengandung flavonoid. Flavonoid merupakan salah satu metabolit sekunder yang dapat memberikan efek antiinflamasi. Penelitian ini bertujuan mengetahui pengaruh penggunaan ekstrak etanol ciplukan sebagai antiinflamasi pada tikus yang diinduksi karagenan. Penelitian ini merupakan penelitian laboratorium eksperimental in vivo menggunakan desain rancangan acak lengkap pada 25 ekor tikus galur Wistar yang terbagi ke dalam lima kelompok. Kelompok kontrol negatif diberi carboxymethilcellulose. Kontrol positif diberi sodium diklofenak 27 mg/200 gBB. Kelompok uji diberi ekstrak etanol ciplukan dengan dosis 3,6 mg/200 gBB; 5,4 mg/200 gBB; dan 7,2 mg/200 gBB. Induksi inflamasi dilakukan dengan menginjeksikan karagenan pada telapak kaki tikus, lalu diukur menggunakan pletismometer dari jam ke-1 hingga jam ke-6. Penelitian ini dilakukan di Laboratorium Farmasi, Universitas Islam Bandung dan Laboratorium Farmasi dan Terapi, Universitas Padjajaran dari bulan Juni hingga September 2019. Volume rerata telapak kaki tikus pada jam ke-6 menggunakan Uji Kruskal-Wallis adalah p=0,02 (p<0,05). Hasil Uji Mann-Whitney diperoleh p<0,05 yang menunjukkan terdapat perbedaan bermakna antara kontrol negatif dan kontrol positif serta kelompok uji. Uji one-way ANOVA pada persentase penghambatan edema antara kontrol positif dan kelompok uji diperoleh p=0,107 yang menunjukkan tidak terdapat perbedaan yang bermakna. Terdapat pengaruh ekstrak etanol ciplukan sebagai antiinflamasi dengan persentase penghambatan edema tertinggi pada dosis 5,4 mg/200 gBB. Kandungan flavonoid pada ciplukan diduga mampu menghambat pembentukan prostaglandin dengan menginhibisi enzim siklooksigenase. Simpulan penelitian ini adalah ekstrak etanol ciplukan dapat digunakan sebagai antiinflamasi.

AKTIVITAS ANTIINFLAMASI EKSTRAK ETANOL DAUN KOPI ARABIKA (Coffea arabica L.) PADA EDEMA TIKUS

<em>The coffee leaf contains flavonoid compounds that are known as an antiinflammation agent. The study aimed to determine antiinflammatory activity of arabica coffee's leaf extract (</em>Coffea arabica<em> L.) against edema on white rat soles of carrageenan-induced rats. The research began with the maceration extraction of coffee leaf in 70% ethanol. The inflammation test was held by measuring the formation of edema using a plethysmometer. The dosages of arabica coffee leaf extract used were 60 mg.kg^-1, 120 mg.kg^-1, and 180 mg.kg^-1 rat weight of white Sprague Dawley rat (</em>Rattus norvegicus<em>). The data were analyzed by Kruskal Wallis and Mann Whitney non-parametric tests. Phytochemical screening showed that arabica coffee leaf extract contained flavonoid, saponin, alkaloid, tannin and triterpenoids compound. The arabica coffee leaf extract showed the best antiinflammatory activity at the dose of 180 mg.kg^-1 rat weight with 71.66% inhibition percentage at the 5^th hour, which was better than the positive control (66.91% edema inhibition at the same hour). This result determined that the leaf extract of arabica coffee had antiinflammatory activity. However, it is necessary to study the acute and chronic toxicity and formulates the arabica coffee leaf extract as a pharmacy product.</em>

Potential Nutraceutical Benefits of In Vivo Grown Saffron (Crocus sativus L.) As Analgesic, Anti-inflammatory, Anticoagulant, and Antidepressant in Mice

Crocus sativus, a medicinally important herbaceous plant, has been traditionally used to cure coughs, colds, insomnia, cramps, asthma, and pain. Moreover, the therapeutic applications of saffron include its immunomodulatory and anticancer properties. The current experimental analysis was performed to explore the potential nutraceutical efficacy of corm, leaf, petal, and stigma of saffron ethanolic extracts as analgesic, anti-inflammatory, anticoagulant, and antidepressant using hot plate, carrageenan-induced paw edema, capillary tube and forced swim test, respectively in mice. The results indicated that among all the extracts, stigma ethanolic extract (SEE) represented maximum latency activity (72.85%) and edema inhibition (77.33%) followed by petal ethanolic extract (PEE) with latency activity and edema inhibition of 64.06 and 70.50%, respectively. Corm ethanolic extract (CEE) and leaf ethanolic extract (LEE) displayed mild analgesic activity of 22.40% and 29.07%, respectively. Additionally, LEE (53.29%) and CEE (47.47%) exhibited mild to moderate response against inflammation. The coagulation time of SEE (101.66 s) was almost equivalent to the standard drug, aspirin (101.66 s), suggesting a strong anticoagulant effect followed by PEE (86.5 s). LEE (66.83 s) represented moderate inhibitory effect on coagulation activity while CEE (42.83 s) showed neutral effect. Additionally, PEE and SEE also expressed itself as potential antidepressants with immobility time ≤76.66 s, while CEE (96.50 s) and LEE (106.83 s) indicated moderate to mild antidepressant efficacy. Based on the in vivo activities, saffron extract, particularly SEE and PEE, can be used as a potential nutraceutical and therapeutic agent due to its significant pharmacological activities.

Biological activity and flavonoid profile of five species of the Bursera genus

Background: The genus Bursera Jacq. ex. L. concentrates its diversity in Mexico. Among the secondary metabolites that can be isolated from organic its extracts are flavonoids and lignans. Research question: Do the biological activity of the hydroalcoholic extracts from five Bursera species studied depend on their flavonoid content? Study site: Oaxaca, Mexico. Methods: The extracts of B. aptera Ramírez, B. fagaroides (Kunth) Engl., B. schlechtendalii Engl., B. galeottiana Engl., B. morelensis Ramírez were analyzed by High Resolution Liquid Chromatography (HPLC) to determine their flavonoid composition. The antiradical DPPH, anti-inflammatory, antibacterial and antifungal activities of the extracts were determined. Results: Phlorizin and quercetin were conserved in both stems and leaves of the five species studied. The phloretin was present only in the leaves of B. aptera. The highest antibacterial activity was observed against Staphylococcus epidermidis and Salmonella typhimurium by the extracts of leaves of B. aptera (MIC 0.002 mg/mL) and the stems of B. fagaroides (MIC 0.015 mg/mL). The extract of stems of B. morelensis against Fusarium boothii presented the highest antifungal effect (lower than 50 ?g/mL). The anti-inflammatory activity of B. fagaroides was 51.24 % edema inhibition (1 mg/ear) compare to 78.76 % of indomethacin (0.358 mg/ear). Conclusion: The presence of flavonoids in five species studied suggests the richness of these compounds in Bursera genus. The biological activities studied indicated the potential medicinal use of these species and the role that the flavonoids play in plant physiology.

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

Bisphosphonic acids (or bisphosphonates) have been successfully used in the clinic treatment of bone diseases for over decades. Additionally, the antiinflammatory activity of these compounds has been gaining attention. In our previous work, we synthesized and in vivo evaluated the bisphosphonic esters 1 and 2, finding a moderate edema inhibition upon oral and topical administration on BALB/c mice. Thus, in this work, the bioisosteric replacement of an amide functional group for an ester afforded the new bisphosphonates 3–6, which had a moderate oral edema inhibition (25 mg/kg dose) and a significant topical antiinflammatory activity (2 mg/ear) on BALB/c mice, with 6 being the most active hit (55.9% edema inhibition), comparable to the positive control (55.5% edema inhibition) on a TPA topical model. Next, to assess the acute toxicity of the synthesized derivatives, test animals were administered with 50–100 mg/kg of 3–6, respectively, by an oral route, and after 14 days, neither lethality nor a significative weight loss were observed. Finally, a structure–activity relationship (SAR) and a molecular docking analysis of 3–6 helped us to explain the trend observed in biological tests. Considering all these aspects, we propose the inhibition of MMP-8 and MMP-9 as a possible action mechanism of the synthesized derivatives.

Effectivity of Holothuria scabra and Spirulina platensis extract combination as an Antiinflammatory Agent Measured by Carrageenan-induced Rat Paw Edema

Sea cucumber, Holothuria scabra, can be found abundantly in Indonesian seas, which is also known to possess several medicinal properties. Spirulina platensis is another marine resources that has recently been extensively researched for its medicinal ability, such as anti-inflammatory effect. This study aims to evaluate the efficacy of H. scabra extract combined with S. platensis extract in reducing inflammation. This study uses male Wistar rats as the study animal. Inflammation was induced by injecting carrageenan solution into the mice paw. Combination of H. scabra and S. platensis extract with various combination ratio (1:1; 1:2; and 2:1) was applied to the mice paw. Diclofenac sodium was used as the standard control therapy. Edema inhibition rate and anti-inflammatory efficacy were measured by analyzing the edema size and calculating the edema difference. Combination of H. scabra and S. platensis with 1:1 ratio has the largest edema inhibition volume compared to the other treatments. H. scabra and S. platensis combination outperforms the positive diclofenac sodium control group in terms of edema inhibition. The highest anti-inflammatory effect is obtained in the combination of H. scabra and S. platensis with 1:2 ratio, however, the anti-inflammatory efficacy is not as potent as the positive control. The effectivity of Holothuria scabra and Spirulina platensis extract in reducing the edema might be caused by their ability to reduce the levels of several inflammatory markers, including IL-6, NO, MMP9, and COX-2. This result suggests that H. scabra and S. platensis combination has anti-inflammatory effect shown in mice paw edema model.

The Anti-Inflammatory Activity of Humic Acid from Borneo Peat Soil in Mice

Humic acid is a humus compound found in peat soil. Humic acid can potentially be used as an anti-inflammatory compound. This study aimed to determine the effect of humic acid on the volume of foot mice edema and to find the best dose that can suppress the degree of edema volume. The animal object was Swiss mice weighing 25-30 grams and 3 months old. The study used Randomized Block Design (RBD) with positive control, negative control and humic acid treatment with dose 62.5 mg kg-1BW, 125 mg kg-1BW, and 250 mg kg-1BW. The result of this research showed that edema inhibition by the administration of humic acid dose 62,5; 125; 250 mg kg-1 had inflammatory inhibition percentage 2.67%, 13.34%, and 20.01% respectively in 5-hour observation. The best dose of humic acid to suppress inflammation in the mice's paw is a humic acid dose of 250 mg kg-1 compared with value 23.3% of sodium diclofenac as the positive control.

New ibuprofen derivatives as H2S and NO donors as safer anti-inflammatory agents

Aim: Nonsteroidal anti-inflammatory drugs are expansively used worldwide. However, their prolonged administration is associated with serious side effects, especially gastrointestinal ulceration. Materials & methods: New ibuprofen derivatives hybridized with H2S- or NO-donating moieties were synthesized and evaluated for their anti-inflammatory activity and ulcerogenic effect. COX-1/COX-2 isozymes selectivity test for the most promising derivatives was performed. Molecular docking studies were performed. Results: Most of the compounds showed promising anti-inflammatory activity comparable to that of ibuprofen (% edema inhibition = 76.6 and ulcer index = 21.26) with much better gastrointestinal tract tolerance (ulcer indices ranging from 0 to 14.67), especially compound 2 -H2S donor- (% edema inhibition = 75.5 and ulcer index = 11.75) and compound 16 -NO donor- (% edema inhibition = 65.4 and ulcer index = 8.66).