The primary reason for cancer-related fatalities is metastasis. The compound 4-carbomethoxyl-10-epigyrosanoldie E, derived from the Sinularia sandensis soft coral species grown in cultures, exhibits properties that counteract inflammation. Moreover, it has been observed to trigger both apoptosis and autophagy within cancerous cells. This research focuses on examining the inhibitory impact of 4-carbomethoxyl-10-epigyrosanoldie E on the migration and invasion processes in Cal-27 and Ca9-22 oral cancer cell lines. To assess how this compound affects cell migration and invasion, the Boyden chamber assay was employed. Furthermore, Western blot analysis was utilized to explore the underlying molecular mechanisms. In a dose-dependent manner, 4-carbomethoxyl-10-epigyrosanoldie E notably decreased the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9, along with urokinase-type plasminogen activator (uPA), in both Cal-27 and Ca9-22 cell lines. Conversely, it elevated the concentrations of tissue inhibitors of metalloproteinases-1 (TIMP-1) and TIMP-2. In addition, the treatment with this compound led to the inhibition of phosphorylation in extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). It also curtailed the expression of several key proteins including focal adhesion kinase (FAK), protein kinase C (PKC), growth factor receptor-bound protein 2 (GRB2), Rac, Ras, Rho A, mitogen-activated protein kinase kinase kinase 3 (MEKK3), and mitogen-activated protein kinase kinase 7 (MKK7). Furthermore, the expression levels of IQ-domain GTPase-activating protein 1 (IQGAP1) and zonula occludens-1 (ZO-1) were significantly reduced by the compound. The ability of 4-carbomethoxyl-10-epigyrosanoldie E to inhibit the migration and invasion of Cal-27 and Ca9-22 oral cancer cells was observed to be dose dependent. This inhibitory effect is primarily attributed to the suppression of MMP-2 and MMP-9 expression, as well as the downregulation of the mitogen-activated protein kinase (MAPK) signaling pathway.

Rou-Yi Fang

Yueh-Wen Liu

Yih-Gang Goan

Jen-Jie Lin

Jui-Hsin Su

Wen-Tung Wu

Yu-Jen Wu

Suppression of Migration and Invasion by 4-Carbomethoxyl-10-Epigyrosanoldie E from the Cultured Soft Coral Sinularia sandensis through the MAPKs Pathway on Oral Cancer Cells

Developing countries face enormous challenges with substandard and falsified antimalarial drugs. One specific issue is the lack of a simple, cost-effective, and robust HPLC method to simultaneously determine and quantify the active pharmaceutical ingredients (APIs) in fixed-dose artemether-lumefantrine pharmaceutical dosage forms. The current study developed a novel, simple, sensitive, precise, accurate, and cost-effective RP-HPLC method for the simultaneous determination and quantification of artemether and lumefantrine in pharmaceutical dosage forms. The HPLC analysis was carried out on an Agilent 1260 Infinity Series HPLC system equipped with an ODS Intersil-C8 (150 × 4.6 mm) 5.0 µm column, by isocratic elution. The mobile phase composition consisted of acetonitrile and 0.05% orthophosphoric acid buffer of pH 3.5 in the ratio of 70 : 30 v/v. The analysis was performed at a 1 mL/min flow rate and a column temperature of 25°C. The total run time was 6 minutes. The detection was done with a variable wavelength detector (VWD) at an isosbestic point wavelength (λ) of 210 nm. The developed method was validated according to the ICH guidelines concerning system suitability, specificity, linearity, accuracy, precision, and robustness. The system suitability of the developed method revealed satisfactory theoretical plates and symmetry factors. The method proved to be specific, with no interference of mobile phase or excipients. The calibration plot exhibited linearity over the concentration range of 275–1925 μg/mL with <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063999pt" id="M1" height="11.7978pt" version="1.1" viewBox="-0.0498162 -11.5914 13.2276 11.7978" width="13.2276pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-83" d="M610 18C585 26 567 34 540 68C517 97 499 128 476 171C452 215 425 276 413 304C496 332 570 394 570 494C570 555 545 595 509 619S419 650 364 650H139L133 622C216 615 219 612 203 527L129 132C112 40 105 36 23 28L17 0H279L285 28C199 34 194 40 211 132L239 284H284C320 284 334 275 351 236C374 182 394 140 420 93C459 23 495 -1 592 -8H600L610 18ZM480 485C480 424 449 372 403 342C374 323 338 316 293 316H245L291 562C296 589 301 601 311 608S337 618 358 618C432 618 480 575 480 485Z"/></g><g transform="matrix(.0091,0,0,-0.0091,8.151,-5.741)"><path id="g50-51" d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z"/></g></svg> = 0.9992 for artemether and a range of 150–1050 μg/mL with <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063999pt" id="M2" height="11.7978pt" version="1.1" viewBox="-0.0498162 -11.5914 13.2276 11.7978" width="13.2276pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-83"/></g><g transform="matrix(.0091,0,0,-0.0091,8.151,-5.741)"><use xlink:href="#g50-51"/></g></svg> = 0.9985 for lumefantrine. The accuracy of the method, determined by the recovery study, was 99.79–100.16% for artemether and 99.04–99.50% for lumefantrine. The % RSD values for intraday precision were 0.175 and 0.203, while interday precision values were 0.340 and 0.554 for artemether and lumefantrine, respectively. The method demonstrated robustness when subjected to slight modifications in the flow rate, column temperature, and mobile phase composition. The developed analytical method proved satisfactory as per ICH guidelines and hence can be used for the determination and quantification of artemether and lumefantrine in bulk drug and pharmaceutical dosage forms.

Simon Nyarko

Kwabena Ofori-Kwakye

Raphael Johnson

Noble Kuntworbe

Desmond Asamoah Bruce Otu

Denis Dekugmen Yar

Yaa Asantewaa Osei

Development of the RP-HPLC Method for Simultaneous Determination and Quantification of Artemether and Lumefantrine in Fixed-Dose Combination Pharmaceutical Dosage Forms

A European legislation was put in place for the reporting of medication errors, and guidelines were drafted to help stakeholders in the reporting, evaluation, and, ultimately, minimization of these errors. As part of pharmacovigilance reporting, a proper classification of medication errors is needed. However, this process can be tedious, time-consuming, and resource-intensive. To fulfill this obligation regarding medication errors, we developed an algorithm that classifies the reported errors in an automated way into four categories: potential medication errors, intercepted medication errors, medication errors without harm (i.e., not associated with adverse reaction(s)), and medication errors with harm (i.e., associated with adverse reaction(s)). A fifth category (“conflicting category”) was created for reported cases that could not be unambiguously classified as either potential or intercepted medication errors. Our algorithm defines medication error categories based on internationally accepted terminology using the Medical Dictionary for Regulatory Activities (MedDRA®) preferred terms. We present the algorithm and the strengths of this automated way of reporting medication errors. We also give examples of visualizations using spontaneously reported vaccination error data associated with the adjuvanted recombinant zoster vaccine. For this purpose, we used a customized web-based platform that uses visualizations to support safety signal detection. The use of the algorithm facilitates and ensures a consistent way of categorizing medication errors with MedDRA® terms, thereby saving time and resources and avoiding the risk of potential mistakes versus manual classification. This allows further assessment and potential prevention of medication errors. In addition, the algorithm is easy to implement and can be used to categorize medication errors from different databases.

Christophe Dessart

Fernanda Tavares-Da-Silva

Lionel Van Holle

Olivia Mahaux

Jens-Ulrich Stegmann

A Model for Monitoring Spontaneously Reported Medication Errors Using the Adjuvanted Recombinant Zoster Vaccine as an Example

Obesity, characterized by excessive adipose tissue accumulation, has emerged as a crucial determinant for a wide range of chronic medical conditions. The identification of effective interventions for obesity is of utmost importance. Widely researched antiobesity agents focus on pancreatic lipase, a significant therapeutic target. This study presented the evaluation of ten flavonoid compounds in terms of their inhibitory activities against pancreatic lipase, utilizing both in vitro and in silico approaches. The results indicated that all tested compounds demonstrated modest and weaker inhibitory activities compared to the reference compound, orlistat. Among the compounds investigated, F01 exhibited the highest potency, with an IC50 value of 17.68 ± 1.43 µM. The enzymatic inhibition kinetic analysis revealed that F01 operated through a competitive inhibition mechanism with a determined <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.291101pt" id="M1" height="11.927pt" version="1.1" viewBox="-0.0498162 -8.6359 12.4199 11.927" width="12.4199pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-76" d="M743 650H503L496 622L527 618C563 613 564 603 532 573C449 495 371 431 323 392C301 374 272 355 246 346L280 522C297 609 300 614 379 622L385 650H135L129 622C209 614 215 609 198 522L124 133C106 39 99 35 23 28L17 0H271L277 28C193 35 192 39 208 133L239 316C264 328 280 325 303 288C368 183 435 90 502 0H652L659 28C602 34 584 43 543 94C495 154 403 283 347 369L574 554C634 603 659 612 735 624L743 650Z"/></g><g transform="matrix(.0091,0,0,-0.0091,9.23,3.132)"><path id="g50-106" d="M250 606C250 634 233 656 203 656C168 656 146 618 146 593C146 564 169 545 192 545C227 545 250 573 250 606ZM227 95L212 119C187 98 152 71 135 71C129 71 128 78 134 102L207 373C219 418 217 451 194 451C165 451 92 411 30 351L44 326C77 353 106 371 114 371C124 371 121 357 117 341L55 97C32 5 46 -12 70 -12C108 -12 191 51 227 95Z"/></g></svg> of 7.16 μM. This value suggested a moderate binding affinity for the pancreatic lipase enzyme. Furthermore, the associated <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-3.2957pt" id="M2" height="11.9316pt" version="1.1" viewBox="-0.0498162 -8.6359 24.0515 11.9316" width="24.0515pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-87" d="M697 650H468L461 623L492 619C539 613 547 605 518 546C481 471 367 264 278 116H276C239 278 197 500 186 567C180 604 185 613 226 619L252 623L260 650H24L17 623C78 617 92 613 108 533L216 -11H247C365 200 515 462 560 529C616 612 624 615 689 623L697 650Z"/></g><g transform="matrix(.0091,0,0,-0.0091,7.332,3.132)"><path id="g58-107" d="M810 0V30C751 35 744 40 744 106V296C744 396 694 451 614 451C583 451 558 438 537 425C512 409 485 391 454 368C434 420 390 451 342 451C309 451 285 439 260 424C228 405 206 387 185 372V453C141 434 90 421 43 413V386C102 378 105 373 105 309V106C105 41 96 35 29 30V0H243V30C194 35 185 41 185 106V335C216 360 256 389 297 389C357 389 384 348 384 275V106C384 41 374 35 312 30V0H530V30C475 35 465 41 465 104V294C465 313 464 324 463 336C502 367 539 389 576 389C637 389 663 346 663 274V109C663 41 653 35 593 30V0H810Z"/></g><g transform="matrix(.0091,0,0,-0.0091,14.894,3.132)"><path id="g58-95" d="M442 39L431 68C420 63 406 57 394 57C377 57 359 71 359 118V301C359 353 349 393 314 424C291 443 261 451 230 451C171 438 107 401 79 381C59 366 46 355 46 340C46 316 72 295 91 295C106 295 117 303 122 319C131 350 139 371 152 384C163 397 178 404 197 404C246 404 281 365 281 293V278C260 262 186 232 124 213C69 194 41 161 41 112C41 47 92 -12 163 -12C195 -12 243 25 283 51C288 35 293 22 308 7C319 -4 339 -12 354 -12L442 39ZM281 87C262 68 226 51 199 51C169 51 129 74 129 126C129 162 151 181 190 198C211 208 259 229 281 240V87Z"/></g><g transform="matrix(.0091,0,0,-0.0091,18.98,3.132)"><path id="g58-118" d="M482 0V30C420 38 407 48 370 103L273 248C308 299 331 332 352 357C387 397 401 404 463 409V439H277V409C318 405 324 400 307 369C290 337 270 307 251 279L194 367C175 396 180 402 220 409V439H18V409C74 401 87 395 117 349L204 213C173 168 147 130 119 95C78 46 67 38 5 30V0H195V30C144 38 143 47 162 79C181 112 202 149 225 181L297 70C314 43 307 35 264 30V0H482Z"/></g></svg> value was quantified at 0.03272 ΔA·min−1. In silico studies revealed that F01 displayed a binding mode similar to that of orlistat, despite lacking an active functional group capable of forming a covalent bond with Ser152 of the catalytic triad. However, F01 formed a hydrogen bond with this crucial amino acid. Furthermore, F01 interacted with other significant residues at the enzyme’s active site, particularly those within the lid domain. Based on these findings, F01 demonstrates substantial potential as a candidate for further investigations.

The-Huan Tran

Thanh-Tan Mai

Thi-Thu-Trang Ho

Thi-Ngoc-Dung Le

Thi-Cam-Nhung Cao

Khac-Minh Thai

Thai-Son Tran

Inhibition of Pancreatic Lipase by Flavonoid Derivatives: In Vitro and In Silico Investigations

This research investigated if pitavastatin (Pita) might protect rats’ kidneys against thioacetamide (TAA). By altering the PTEN/AKT/mTOR pathway, pitavastatin may boost kidney antioxidant capacity and minimize oxidative damage. Statins have several benefits, including antioxidant and anti-inflammatory characteristics. The principal hypothesis of this study was that Pita can regulate the miR-93/PTEN/AKT/mTOR pathways, which is thought to be responsible for its renoprotective effects. The experiment divided male rats into four groups. Group 1 included untreated rats as the control. Group 2 included rats which received TAA (100 mg/kg intraperitoneally thrice a week for two weeks) to destroy their kidneys. Groups 3 and 4 included rats which received Pita orally at 0.4 and 0.8 mg/kg for 14 days after TAA injections. Renal injury increased BUN, creatinine, and MDA levels and decreased glutathione (GSH) levels. Pitavastatin prevented these alterations. TAA decreased PTEN and increased miR-93, Akt, p-Akt, mTOR, and Stat3 in the kidneys. Pitavastatin also regulated the associated culprit pathway, miR-93/PTEN/Akt/mTOR. In addition, TAA induced adverse effects on the kidney tissue, which were significantly ameliorated by pitavastatin treatment. The findings suggest that pitavastatin can attenuate renal injury, likely by regulating the miR-93/PTEN/Akt/mTOR pathway. This modulation of the pathway appears to contribute to the protective effects of pitavastatin against TAA-induced renal injury, adding to the growing evidence of the pleiotropic benefits of statins in renal health.

Marawan A. Elbaset

Bassim M. S. A. Mohamed

Passant E. Moustafa

Tuba Esatbeyoglu

Sherif M. Afifi

Alyaa F. Hessin

Sahar S. Abdelrahman

Hany M. Fayed

Renoprotective Effect of Pitavastatin against TAA-Induced Renal Injury: Involvement of the miR-93/PTEN/AKT/mTOR Pathway

Background. The increase in the number of drug-resistant Plasmodium species continues to be a serious public health concern. Therefore, identification of the potential novel antimalarial drugs derived from therapeutic plants could help solve this issue. This study investigated whether Cyperus rotundus aqueous crude extract (CRE) and its combination with dihydroartemisinin (DHA) were effective against Plasmodium berghei ANKA-infected mice. Methods. CRE was prepared from C. rotundus rhizomes and evaluated using acute and subacute toxicity tests on BALB/c mice. The antimalarial effectiveness of CRE was assessed at 100, 200, and 400 mg/kg in a 4-day suppressive test with curative and prophylactic testing and measurement of packed cell volume (PCV), body weight (BW), rectal temperature, and mean survival time (MST). Results. Following acute and subacute treatment, CRE caused no harmful effects or mortality in mice. When compared with that in the untreated control, infected mice administered with 400 mg/kg of CRE in a 4-day suppressive test exhibited the strongest antimalarial activity (55.30% inhibition) with prolonged MST. However, curative and prophylactic assays did not reveal CRE to have antimalarial activity. In comparison with that achieved with the single therapy, the combination of DHA and CRE at ED50/2 (1 and 200 mg/kg, respectively) produced considerable antimalarial activity at 90.08% inhibition with synergism (combination index = 0.21701). For the other parameters, CRE administration prevented malarial-induced changes in PCV, BW, and rectal temperature. Conclusions. CRE treatment significantly inhibited malaria in the 4-day suppressive test, and CRE combined with DHA had a synergistic antimalarial effect.

Sakaewan Ounjaijean

Charupa Lektip

Voravuth Somsak

In Vivo Antimalarial Activity of Cyperus rotundus and Its Combination with Dihydroartemisinin against Plasmodium berghei

Background. The emergence of drug-resistant parasites impedes disease management and eradication efforts. Hence, a reinvigorated attempt to search for potent lead compounds in the mangroves is imperative. Aim. This study evaluates in vitro antiplasmodial activity, antioxidant properties, and cytotoxicity of A. africana leaf alkaloidal extracts. Methods. The A. africana leaves were macerated with 70% ethanol to obtain a total crude extract. Dichloromethane and chloroform-isopropanol (3 : 1, v/v) were used to extract the crude alkaloids and quaternary alkaloids from the total crude. The antiplasmodial activities of the alkaloidal extracts were performed against 3D7 P. falciparum chloroquine-sensitive clone via the SYBR Green I fluorescence assay with artesunate serving as the reference drug. The alkaloidal extracts were further evaluated for antioxidant properties via the total antioxidant capacity (TAC), the total glutathione concentration (GSH), the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, and the ferric-reducing antioxidant power (FRAP) methods. The cytotoxic activity of the alkaloidal extracts was tested on erythrocytes using a 3-(4,5-dimethylthiazol-2-yl)-5-diphenyltetrazolium bromide-MTT assay with little modification. The phytocompounds in the alkaloidal extracts were identified via gas chromatography-mass spectrometry (GC-MS) techniques. Results. The total crude extract showed good antiplasmodial activity (IC50 = 11.890 µg/mL). The crude and quaternary alkaloidal extracts demonstrated promising antiplasmodial effects with IC50 values of 6.217 and 6.285 µg/mL, respectively. The total crude and alkaloidal extracts showed good antioxidant properties with negligible cytotoxicity on erythrocytes with good selectivity indices. The GC-MS spectral analysis of crude alkaloidal extracts gave indole and isoquinoline alkaloids and several other compounds. Dexrazoxane was found to be the main compound predicted, with an 86% peak area in the quaternary alkaloidal extract. Conclusion. The crude and quaternary alkaloidal extracts exhibited antiplasmodial activities and ability to inhibit oxidative stress with negligible toxicity on erythrocytes. This may be good characteristics to avoid oxidative stress related to Plasmodium infection in the treatment of malaria.

Mustapha A. Ahmed

Elvis O. Ameyaw

Francis A. Armah

Patrick M. Fynn

Isaac Asiamah

George Ghartey-Kwansah

Felix K. Zoiku

Ebenezer Ofori-Attah

Christian K. Adokoh

Alkaloidal Extracts from Avicennia africana P. Beauv. (Avicenniaceae) Leaf: An Antiplasmodial, Antioxidant, and Erythrocyte Viable

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Advances in Pharmacological and Pharmaceutical Sciences publishes original research articles and&nbsp;review articles in all areas of experimental and clinical pharmacology, pharmaceutics, medicinal chemistry and drug delivery.

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Advances in Pharmacological and Pharmaceutical Sciences publishes original research articles and review articles in all areas of experimental and clinical pharmacology, pharmaceutics, medicinal chemistry and drug delivery.

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