Contemporary Insights into the Biological Mechanisms of Parkia biglobosa.

For a long time, traditional medicine has relied on the use of medicinal plants and herbal products which have served as the basis for numerous pharmaceuticals. Parkia biglobosa (Jacq) R.Br.ex. G. Don., commonly called the African locust bean tree, is a perennial deciduous plant native to West Africa where it is highly esteemed for its nutritional and traditional medicinal benefits. Parkia biglobosa's ethnomedicinal uses include microbial infections such as diarrhea and chronic diseases like hypertension and type 2 diabetes mellitus. This article presents the current understanding of the molecular mechanisms underlying Parkia biglobosa's biological effects. An electronic database search was conducted using P. biglobosa and its synonyms as keywords in Scientific Electronic Library Online, ISI Web of Knowledge, PubMed, Scopus, Science Direct, and Google Scholar. Consistently, scientific research has confirmed the medicinal effects of the plant's extracts and active phytochemicals, including antimicrobial, analgesic, antidiabetic, antihypertensive, hypolipidemic, and neuroprotective properties, among others. It highlights the contributions of identified innate phytochemicals and existing limitations to therapeutic applications, as well as the need for and prospects for further research. Advancing our understanding of the medicinal plant's biological mechanisms and the contributions of the active phytochemicals would allow for more effective exploration of its vast pharmacological potential and facilitate clinical applications.

CXC Chemokines in the Pathogenesis of Pulmonary Disease and Pharmacological Relevance.

Chemokines and their receptors play important roles in the pathophysiology of many diseases by regulating the cellular migration of major inflammatory and immune players. The CXC motif chemokine subfamily is the second largest family, and it is further subdivided into ELR motif CXC (ELR+) and non-ELR motif (ELR-) CXC chemokines, which are effective chemoattractants for neutrophils and lymphocytes/monocytes, respectively. These chemokines and their receptors are expected to have a significant impact on a wide range of lung diseases, many of which have inflammatory or immunological underpinnings. As a result, manipulations of this subfamily of chemokines and their receptors using small molecular agents and other means have been explored for potential therapeutic benefit in the setting of several lung pathologies. Furthermore, encouraging preclinical data has necessitated the progression of a few of these drugs into clinical trials in order to make the most effective use of interventions in the development of viable targeted therapeutics. The current review presents the understanding of the roles of CXC ligands (CXCLs) and their cognate receptors (CXCRs) in the pathogenesis of several lung diseases such as allergic rhinitis, COPD, lung fibrosis, lung cancer, pneumonia, and tuberculosis. The potential therapeutic benefits of pharmacological or other CXCL/CXCR axis manipulations are also discussed.

Coronavirus Disease 2019 and Herbal Therapy: Pertinent Issues Relating to Toxicity and Standardization of Phytopharmaceuticals.

Coronavirus disease 2019 (COVID-19) is a virulent viral disease that has now become a public health emergency of global significance and still without an approved treatment regimen or cure. In the absence of curative drugs and with vaccines development still in progress, alternative approaches to stem the tide of the pandemic are being considered. The potential of a phytotherapeutic approach in the management of the dreaded disease has gained attention, especially in developing countries, with several claims of the development of anti-COVID-19 herbal formulations. This is a plausible approach especially with the increasing acceptance of herbal medicine in both alternative and orthodox medical practices worldwide. Also, the established efficacy of herbal remedies in the treatment of numerous viral diseases including those caused by coronaviruses, as well as diseases with symptoms associated with COVID-19, presents a valid case for serious consideration of herbal medicine in the treatment of COVID-19. However, there are legitimate concerns and daunting challenges with the use of herbs and herbal products. These include issues of quality control, unethical production practice, inadequate information on the composition, use and mechanisms, weak regulatory policies, herb-drug interactions and adverse reactions, and the tendency for abuse. This review discusses the feasibility of intervention with herbal medicine in the COVID-19 pandemic and the need to take proactive measures to protect public health by improving the quality and safety of herbal medicine deployed to combat the disease. Graphical abstract. Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-021-00132-x.

Prevalence of COVID-19 Diagnostic Output with Chest Computed Tomography: A Systematic Review and Meta-Analysis.

BACKGROUND: The pooled prevalence of chest computed tomography (CT) abnormalities and other detailed analysis related to patients' biodata like gender and different age groups have not been previously described for patients with coronavirus disease 2019 (COVID-19), thus necessitating this study. Objectives: To perform a meta-analysis to evaluate the diagnostic performance of chest CT, common CT morphological abnormalities, disease prevalence, biodata information, and gender prevalence of patients. METHODS: Studies were identified by searching PubMed and Science Direct libraries from 1 January 2020 to 30 April 2020. Pooled CT positive rate of COVID-19 and RT-PCR, CT-imaging features, history of exposure, and biodata information were estimated using the quality effect (QE) model. RESULTS: Out of 36 studies included, the sensitivity was 89% (95% CI: 80-96%) and 98% (95% CI: 90-100%) for chest CT and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The pooled prevalence across lesion distribution were 72% (95% CI: 62-80%), 92% (95% CI: 84-97%) for lung lobe, 88% (95% CI: 81-93%) for patients with history of exposure, and 91% (95% CI: 85-96%) for patients with all categories of symptoms. Seventy-six percent (95% CI: 67-83%) had age distribution across four age groups, while the pooled prevalence was higher in the male with 54% (95% CI: 50-57%) and 46% (95% CI: 43-50%) in the female. CONCLUSIONS: The sensitivity of RT-PCR was higher than chest CT, and disease prevalence appears relatively higher in the elderly and males than children and females, respectively.

Nutritional benefits, phytochemical constituents, ethnomedicinal uses and biological properties of Miracle fruit plant (Synsepalum dulcificum Shumach. & Thonn. Daniell).

Miracle fruit plant or Miracle berry plant (Synsepalum dulcificum) is a peculiar medicinal plant because of the unique taste-modifying property of its fruit which is due to the presence of the glycoprotein, miraculin. This property has been known for centuries to the people of tropical Western and Central Africa who also employ different parts of the plant in the management of various ailments. Scientific investigations have unravelled several pharmacological properties of the plant which include antidiabetic, blood cholesterol-lowering, anti-hyperuricaemia, antioxidant, anticonvulsant and anticancer properties. Also, subacute administration of the plant extract up to 200 mg/kg was not found to be toxic in rats. Apart from miraculin, other pharmacologically active compounds have been identified in the plant including alkaloids (dihydro-feruloyl-5-methoxytyramine, N-cis-caffeoyltyramine, N-cis-feruloyl-tyramine), lignins (+-syringaresinol, +-epi-syringaresinol), phytosterols, triterpenoids, phenolic acids, flavonoids, and amino acids. The plant has also been credited with notable nutritional benefits. Proper documentation of available information on folkloric use, biological activity, constituent phytocompounds, and nutritional benefits of ethnobotanicals will go a long way in affording optimal benefits from their therapeutic potentials. This can also aid in the conservation of species at risk of extinction. This work presents an up-to-date review of the ethnobotany, phytochemistry, biological and nutritional properties of Synsepalum dulcificum.

Angiotensin-1-converting enzyme inhibition, antioxidant activity, and modulation of cerebral Na+/K+ ATPase by free phenolics of African locust bean (Parkia biglobosa).

AIMS: To investigate the antioxidant activities and effects of free phenols (FPPB) and bound phenols (BPPB) of Parkia biglobosa leaves on some enzymes of neuro-cardiovascular relevance. METHODS AND RESULTS: HPLC-DAD fingerprinting of FPPB and BPPB, and the antihemolytic, radical (1,1-diphenyl-2 picrylhydrazyl, DPPH; 2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid), ABTS) scavenging and ferric reducing antioxidant properties of extracts, were assessed. In addition, the effects of the phenolics on angiotensin-1-converting enzyme (ACE), cerebral acetylcholinesterase/butyrylcholinesterase (AChE/BuChE), and Na+/K+ATPase were determined in vitro. FPPB was more potent than BPPB in terms of ABTS (EC50:4.06 ± 0.3 vs 24.07 ± 2.1 µg/mL) and DPPH (EC50:3.82 ± 0.2 vs 10.22 ± 0.1 µg/mL) radicals scavenged, respectively. The free phenolic extract was a better DPPH. scavenger than ascorbic acid (EC50 = 12.58 ± 0.4 µg/mL; DPPH reference) and compared well with Trolox (EC50:4.44 ± 0.08 µg/mL; ABTS reference). The anti-hemolytic effect of FPPB (36%) and BPPB (53%) was highest at 15 µg/mL but lower than that recorded for ascorbic acid (67% at 10 µg/mL). Even though FPPB (IC50 = 15.35 ± 4.0 µg/mL) and BPPB (IC50 = 46.85 ± 3.3 µg/mL) showed considerably lower ACE-inhibitory effect than ramipril (IC50:0.173 ± 0.04 µg/mL), both extracts demonstrated dose-dependent, significant (p < 0.01/p < 0.05) inhibition of the enzyme. FPPB increased cerebral Na+/K+ATPase activity but neither phenolic extract affects cerebral AChE/BuChE activities. HPLC-DAD revealed catechin, caffeic acid, and quercetin, respectively, as the major phenolics (mg/g) in FPPB (29.85, 30.29, and 17.10) and BPPB (32.70, 30.51, and 19.25). CONCLUSION: The effects of P biglobosa on ACE and cerebral ATPase are related to its constituent phenolics. ACE inhibition could be an important mechanism underlying the documented hypotensive effect of the plant.

Antioxidant activity and protective effects of cocoa and kola nut mistletoe (Globimetula cupulata) against ischemia/reperfusion injury in Langendorff-perfused rat hearts.

Protection against cardiomyocyte damage following ischemia/reperfusion (I/R) injury is highly desirable in patients with ischemic heart disease. Hydromethanol extracts of Globimetula cupulata (mistletoe) growing on cocoa (CGCE) and kola nut (KGCE) trees were assessed for antioxidant content and cardioprotective potential against I/R. Graded concentrations (1-50 µg/mL) of CGCE or KGCE were tested on Langendorff-perfused rat hearts to evaluate the effects on the flow rate, heart rate, and force of cardiac contraction, while another set of hearts were subjected to biochemical analyses. Both extracts showed good antioxidant content and activity, but KGCE (EC50: 24.8±1.8 µg/mL) showed higher hydroxyl radical scavenging activity than CGCE (70.2±4.5 µg/mL). Both extracts at 3 µg/mL reversed (p < 0.001) membrane peroxidation and the significant decrease in nitrite level, coronary flow rate, and superoxide dismutase and catalase activity caused by the I/R cycle. It is concluded that G. cupulata protects against ischemia-reperfusion injury in rat hearts via augmenting endogenous antioxidants and significant restoration of altered hemodynamic parameters.

Effect of homopterocarpin, an isoflavonoid from Pterocarpus erinaceus, on indices of liver injury and oxidative stress in acetaminophen-provoked hepatotoxicity.

BACKGROUND: Novel hepatoprotectives are needed to address the increasing cases of liver problems worldwide. Pterocarpus erinaceus Poir (Fabaceae) ethanol stem bark extract (PE) and its constituent flavonoid, homopterocarpin (HP), were investigated for their protective property in acetaminophen-induced oxidative stress and liver damage. METHODS: Adult male albino rats were divided into nine groups. Seven groups were pretreated with PE (50-, 100-, and 150 mg/kg), HP (25-, 50-, and 75 mg/kg) or silymarin (25 mg/kg), respectively, once daily for 5 consecutive days and then administered acetaminophen (2 g/kg) on the 5th day. The control and acetaminophen-intoxicated groups received normal saline throughout the experimental period, with the latter group additionally receiving 2 g/kg acetaminophen on the 5th day. Administrations were performed po. RESULTS: In the acetaminophen-intoxicated group, there were significant increases (p<0.05) in serum activities of alanine aminotransferase (31.72±3.3 vs. 22.1±1.2 U/I), aspartate aminotransferase (185.1±10.1 vs. 103.83±13.3 U/I), bilirubin level and hepatic malondialdehyde (2.32±0.3 vs. 1.42±0.1 units/mg protein), accompanied with significant decreases (p<0.05) in hepatic reduced glutathione level (0.10±0.01 vs. 0.23±0.03 units/mg protein) and glutathione peroxidase activity (2.51±0.2 vs. 3.25±0.2 µmol H2O2 consumed/min/mg protein) compared with the control. CONCLUSIONS: PE and HP ameliorated most of the observed biochemical alterations with HP appearing to show more potency. The results suggest that the flavonoid, homopterocarpin contributes to the hepatoprotective and antioxidant potentials of P. erinaceus extract.

Protective effects of Parinari curatellifolia flavonoids against acetaminophen-induced hepatic necrosis in rats.

In the present study, we investigated the hepatoprotective potential of Parinari curatellifolia Planch (Chrysobalanaceae) in experimental rats in order to ascertain the validity of folkloric claims of its effectiveness in the treatment of hepatic-related disorders. Flavonoid extract of P. curatellifolia seed, PCF (10-, 20- or 30 mg/kg body weight) or silymarin (25 mg/kg), dissolved in corn oil, was administered by gavage to experimental animals once daily for 14 consecutive days before liver damage was chemically induced through the administration of acetaminophen (2 g/kg p.o.) on the 14th day. Hepatoprotection was assessed by analyzing liver homogenate and serum for markers of hepatotoxicity - alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) activities as well as prothrombin time (PT). Evaluation of biochemical indices of oxidative stress - level of lipid peroxides (LPO), activities of superoxide dismutase (SOD) and catalase, along with histological assessment of hepatic tissue sections were also carried out. Results revealed that all doses of PCF significantly (P < 0.001) and dose dependently prevented acetaminophen-induced increase in serum activities of hepatic enzymes (ALT, AST, GGT, LDH) and PT. Furthermore, PCF (10- and 20 mg/kg) significantly (P < 0.001) reduced lipid peroxidation in liver tissue and restored the activities of the antioxidant enzymes SOD and catalase toward normal levels. Histopathology of the liver tissue showed that PCF mitigated the toxicant-induced hepatocellular necrosis, reduced inflammatory cell infiltration and enhanced hepatocyte regeneration. The results indicated that P. curatellifolia flavonoids demonstrated remarkable hepatoprotective activity in acute liver injury caused by acetaminophen.

Parkia biglobosa improves mitochondrial functioning and protects against neurotoxic agents in rat brain hippocampal slices.

OBJECTIVE: Methanolic leaf extracts of Parkia biglobosa, PBE, and one of its major polyphenolic constituents, catechin, were investigated for their protective effects against neurotoxicity induced by different agents on rat brain hippocampal slices and isolated mitochondria. METHODS: Hippocampal slices were preincubated with PBE (25, 50, 100, or 200 µg/mL) or catechin (1, 5, or 10 µg/mL) for 30 min followed by further incubation with 300 µM H2O2, 300 µM SNP, or 200 µM PbCl2 for 1 h. Effects of PBE and catechin on SNP- or CaCl2-induced brain mitochondrial ROS formation and mitochondrial membrane potential (ΔΨm) were also determined. RESULTS: PBE and catechin decreased basal ROS generation in slices and blunted the prooxidant effects of neurotoxicants on membrane lipid peroxidation and nonprotein thiol contents. PBE rescued hippocampal cellular viability from SNP damage and caused a significant boost in hippocampus Na(+), K(+)-ATPase activity but with no effect on the acetylcholinesterase activity. Both PBE and catechin also mitigated SNP- or CaCl2-dependent mitochondrial ROS generation. Measurement by safranine fluorescence however showed that the mild depolarization of the ΔΨm by PBE was independent of catechin. CONCLUSION: The results suggest that the neuroprotective effect of PBE is dependent on its constituent antioxidants and mild mitochondrial depolarization propensity.

In vitro antioxidant activity and effect of Parkia biglobosa bark extract on mitochondrial redox status.

Aqueous-methanolic extract of Parkia biglobosa bark (PBB) was screened for its polyphenolic constituents, in vitro antioxidant activity, and effect on mitochondria redox status. The in vitro antioxidant activity was assessed by using the scavenging abilities and the reducing powers of 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) diammonium salt radical cation against Fe(3+). Subsequently, the ability of PBB to inhibit lipid peroxidation induced by FeSO(4) (10 µm) and its metal-chelating potential were investigated. The effects of the extract on basal reactive oxygen species (ROS) generation and on the mitochondrial membrane potential (ΔΨm) in isolated mitochondria were determined by using 2', 7'-dichlorodihydrofluorescin (DCFH) oxidation and safranin fluorescence, respectively. PBB mitigated the Fe(II)-induced lipid peroxidation in rat tissues and showed dose-dependent scavenging of DPPH (IC(50): 98.33 ± 10.0 µg/mL) and ABTS. (trolox equivalent antioxidant concentration, TEAC value = 0.05), with considerable ferric-reducing and moderate metal-chelating abilities. PBB caused slight decreases in both the liver and the brain mitochondria potentials and resulted in a significant decrease (p < 0.001) in DCFH oxidation. Screening for polyphenolics using high-performance liquid chromatography coupled to a diode array detector (HPLC-DAD) revealed the presence of caffeic acid, gallic acid, catechin, epigalocatechin, rutin, and quercetin. These results demonstrate for the first time the considerable in vitro antioxidant activity and favorable effect of PBB on mitochondria redox status and provide justification for the use of the plant in ethnomedicine.