A Review of Medicinal Plants with Antiviral Activity Available in Bangladesh and Mechanistic Insight Into Their Bioactive Metabolites on SARS-CoV-2, HIV and HBV.

Currently, viral infection is the most serious health issue which causing unexpected higher rate of death globally. Many viruses are not yet curable, such as corona virus-2 (SARS-CoV-2), human immunodeficiency virus (HIV), hepatitis virus, human papilloma virus and so others. Furthermore, the toxicities and ineffective responses to resistant strains of synthetic antiviral drugs have reinforced the search of effective and alternative treatment options, such as plant-derived antiviral drug molecules. Therefore, in the present review, an attempt has been taken to summarize the medicinal plants reported for exhibiting antiviral activities available in Bangladesh along with discussing the mechanistic insights into their bioactive components against three most hazardous viruses, namely SARS-CoV-2, HIV, and HBV. The review covers 46 medicinal plants with antiviral activity from 25 families. Among the reported 79 bioactive compounds having antiviral activities isolated from these plants, about 37 of them have been reported for significant activities against varieties of viruses. Hesperidin, apigenin, luteolin, seselin, 6-gingerol, humulene epoxide, quercetin, kaempferol, curcumin, and epigallocatechin-3-gallate (EGCG) have been reported to inhibit multiple molecular targets of SARS-CoV-2 viral replication in a number of in silico investigations. Besides, numerous in silico, in vitro, and in vivo bioassays have been demonstrated that EGCG, anolignan-A, and B, ajoene, curcumin, and oleanolic acid exhibit anti-HIV activity while piperine, ursolic acid, oleanolic acid, (+)-cycloolivil-4'-O-ß-d-glucopyranoside, quercetin, EGCG, kaempferol, aloin, apigenin, rosmarinic acid, andrographolide, and hesperidin possess anti-HBV activity. Thus, the antiviral medicinal plants and the isolated bioactive compounds may be considered for further advanced investigations with the aim of the development of effective and affordable antiviral drugs.

Impact of high dose of baricitinib in severe COVID-19 pneumonia: a prospective cohort study in Bangladesh.

PURPOSE: Hyperinflammation in severe COVID-19 infection increases the risk of respiratory failure and one of the cogent reasons of mortality associated with COVID-19. Baricitinib, a janus kinases inhibitor, can potentially suppress inflammatory cascades in severe COVID-19 pneumonia. METHODS: The objective of this study was to compare the clinical outcomes of high dose of baricitinib with its usual dose in patients with severe COVID-19 pneumonia. This prospective cohort study was conducted on 238 adult patients with severe COVID-19 pneumonia. Eight milligram and 4 mg of baricitinib was given orally to 122 patients in the high dose (HD) group and 116 patients the usual dose (UD) group, respectively daily for 14 days, and clinical outcomes were compared among the groups. RESULTS: Blood oxygen saturation level was stabilized (≥94% on room air) earlier in the HD group compared to the UD group [5 (IQR: 4-5)/8 (IQR: 6-9), P < 0.05]. Patients in the HD group required intensive care unit (ICU) and intubation supports more in the UD group than that in patients of the HD group [17.2%/9%, P < 0.05; 11.2%/4.1%, P > 0.05; N = 116/122, respectively]. The 30-day mortality and 60-day rehospitalization rate were higher in the UD group than the HD group [6%/3.3%, P < 0.01; 11.9%/7.6%, P > 0.05; N = 116/122, respectively]. CONCLUSION: The daily high dose of baricitinib in severe COVID-19 results in early stabilization of the respiratory functions, declined requirements of critical care supports, reduced rehospitalization with mortality rate compared to its daily usual dose.

Phytochemical investigations and antioxidant potential of roots of Leea macrophylla (Roxb.).

BACKGROUND: Oleanolic acid (NZ-15), 7 α, 28-olean diol (NZ-38) and Stigmasterol (NZ-14) were isolated from the ethanolic extracts of the roots of Leea macrophylla (Family: Leeaceae) by using chromatographic analysis. This is the first report of isolation of these compounds from this plant. Their structures were constructed by spectroscopic analysis and by comparing the data with the published one. Subsequently the ethanolic extract was fractionated with two organic solvents and all the fractions were studied to evaluate their in vitro antioxidant property. METHODS: The ethanolic extract was fractionated with two organic solvents and all the fractions were studied to evaluate their in vitro antioxidant property by DPPH free radical scavenging assay, superoxide anion radical scavenging assay, nitric oxide radical scavenging assay, and reducing power assay. RESULTS: In the DPPH free radical scavenging assay and superoxide radical scavenging assay, the ethyl acetate soluble fraction of ethanolic extract revealed the highest free radical scavenging activity with IC50 value of 2.65 and 155.62 µg/ml, respectively as compared to standard ascorbic acid (IC50 value of 5.8 and 99.66 µg/ml). Ethyl acetate fraction also possessed highest reducing power activity with an EC50 value of 15.27 µg/ml compared to ascorbic acid (EC50 0.91 µg/ml). On the other hand, the carbon tetrachloride fraction exhibited most significant NO scavenging activity with IC50 value of 277.8 µg/ml that was even higher than that of standard ascorbic acid (IC50 value 356.04 µg/ml). In addition, the total phenolic contents of these extract and fractions were evaluated using Folin-Ciocalteu reagent and varied from 7.93 to 50.21 mg/g dry weight expressed as gallic acid equivalents (GAE). CONCLUSIONS: This study showed that different extracts of roots of L. macrophylla possess potential DPPH, superoxide, and NO free radical scavenging activities. The antioxidant activities of the plant extracts might be due to the presence of oleanolic acid, oleanolic acid derivative 7 α, 28-olean diol and stigmasterol.

Evaluation of analgesic, anti-inflammatory, thrombolytic and hepatoprotective activities of roots of Premna esculenta (Roxb).

BACKGROUND: The objective of this study was to investigate the antinociceptive, anti-inflammatory, thrombolytic and hepatoprotective activities of root extracts of Premna esculenta (family: Verbenaceae). METHODS: The analgesic activity was evaluated using the acetic-acid-induced writhing test in mice and radiant heat tail-flick method in rats. The anti-inflammatory activity was investigated by carrageenan-induced rat's paw edema, while the thrombolytic activity was evaluated by in vitro clot lysis model. The hepatoprotective activity was investigated against carbon-tetrachloride-induced liver damage in rats. RESULTS: In acetic-acid-induced writhing test, chloroform and ethyl acetate fraction of ethanolic extract at a dose of 200 mg/kg showed a significant (p<0.001) reduction in the number of writhes with 85.96% and 61.98% of inhibition, respectively. In radiant heat tail-flick method, the ethanolic extract produced 88.49% (p<0.001) elongation of tail-flicking time at 90 min after oral administration at same dose level. In the carrageenan-induced edema test, the ethanolic extract at a dose of 200 mg/kg showed a significant inhibition of paw edema with 22.68% and 17.24% inhibition after the first and third hours of the study period, respectively. In clot lysis model, the ethanolic extract at 5 mg/mL induced a significant clot lysis activity (37.69%, p<0.001). Oral administration of ethanolic extract at the dose of 400 mg/kg/day for 7 days significantly (p<0.001) reduced the elevated levels of serum glutamic pyruvic transaminase, serum glutamyl oxaloacetate transaminase and alkaline phosphatase compared to the CCl4-treated control group. CONCLUSIONS: The results of the study demonstrated the antinociceptive, anti-inflammatory, thrombolytic and hepatoprotective activities of roots of P. esculenta.

Advances in herbal medicine for treatment of ischemic brain injury.

Ischemic brain injury is one of the leading causes of death worldwide and has attracted a lot of attention in the field of drug discovery. Cerebral ischemia is a complex pathological process involving a series of mechanisms, including generation of free radicals, oxidative stress, disruption of the membrane function, release of neurotransmitters and apoptosis. Thrombolytic therapy is the most effective therapeutic strategy, but the benefits are far from being absolute. Increased attention in the field of drug discovery has been focused on using natural compounds from traditional medicinal herbs for neuroprotection, which appears to be a promising therapeutic option for cerebral ischemia with minimal systemic adverse effects that could limit their long term use. The scenario calls for extensive investigations which can result in the development of lead molecules for neuroprotection in the future. In this context, the present review focuses on possible mechanisms underlying the beneficial effects of herbal drugs in patients with cerebral ischemic injury. Natural compounds have been demonstrated to have neurofunctional regulatory actions with antioxidative, anti-inflammatory, calcium antagonizing and anti-apoptotic activities. Among the several leads obtained from plant sources as potential neuroprotective agents, resveratrol, EGb761, curcumin and epigallocatechin-3-gallate have shown significant therapeutic benefits in cerebral ischemic conditions. However, ligustilide, tanshinone, scutellarin and shikonin are the few lead molecules which are under investigation for treatment of cerebral ischemia.

Antinociceptive, anti-inflammatory, antimicrobial and central nervous system depressant activities of ethanolic extract of leaves and roots of Gomphostemma parviflorum var. parviflorum wall.

BACKGROUND: Gomphostemma parviflorum (Lamiaceae) is a medicinal plant of Bangladesh which has been used traditionally in the treatment of painful and inflammatory conditions such as asthma, headache, fever, etc. OBJECTIVE: To investigate the antinociceptive, anti-inflammatory, central nervous system (CNS) depressant and antimicrobial activities of ethanolic extracts of leaves (GPLE) and roots (GPRE) of the plant. MATERIALS AND METHODS: The antinociceptive potentials of the extracts were studied using acetic acid-induced writhing test in mice, anti-inflammatory activity was investigated using carrageenan-induced paw edema in rats, CNS depressant activities were evaluated using pentobarbitone-induced sleeping time, Hole cross and Open field tests in mice while the anti-microbial activity was studied by in vitro disc diffusion method. RESULTS: The extracts GPLE and GPRE significantly (P < 0.001) and dose dependently inhibited the acetic acid-induced writhing in mice with 73.15% and 53.69% inhibition, respectively at the dose of 200 mg/kg. At the same dose GPLE and GPRE significantly inhibited carrageenan-induced rats paw edema at the end of 4 hour with 35.54% and 28.17% inhibition, respectively. The extracts significantly prolonged the pentobarbitone-induced sleeping time and decreased the locomotory activities in open field and Hole cross tests in mice. The GPLE showed strong antimicrobial activity against Gram-positive and Gram-negative bacteria with zones of inhibition ranging from 8 to 20 mm at a concentration of 400 µg/disc. CONCLUSION: The findings of the study indicate that the leaves and roots of G. parviflorum possess antinociceptive, anti-inflammatory and CNS depressant activity and revealed the antimicrobial activities of leaves extract of the plant. The results justify the traditional use of the plant in the treatment of painful and inflammatory disorders.

A comprehensive situation assessment of injection practices in primary health care hospitals in Bangladesh.

BACKGROUND: Understanding injection practices is crucial for evidence-based development of intervention initiatives. This study explored the extent of injection use and injection safety practices in primary care hospitals in Bangladesh. METHODS: The study employed both quantitative and qualitative research methods. The methods used were--a retrospective audit of prescriptions (n = 4320), focus group discussions (six with 43 participants), in-depth interviews (n = 38) with a range service providers, and systematic observation of the activities of injection providers (n = 120), waste handlers (n = 48) and hospital facilities (n = 24). Quantitative and qualitative data were assessed with statistical and thematic analysis, respectively, and then combined. RESULTS: As many as 78% of our study sample (n = 4230) received an injection. The most commonly prescribed injections (n = 3354) including antibiotics (78.3%), IV fluids (38.6%), analgesics/pain killers (29.4%), vitamins (26.7%), and anti-histamines (18.5%). Further, 43.7% (n = 1145) of the prescribed antibiotics (n = 2626) were given to treat diarrhea and 42.3% (n = 600) of IV fluids (n = 1295) were used to manage general weakness conditions. Nearly one-third (29.8%; n = 36/120) of injection providers reported needle-stick injuries in the last 6 months with highest incidences in Rajshahi division followed by Dhaka division. Disposal of injection needles, syringes and other materials was not done properly in 83.5% (n = 20/24) of the facilities. Health providers' safety concerns were not addressed properly; only 23% (n = 28/120) of the health providers and 4.2% (n = 2/48) of the waste handlers were fully immunized against Hepatitis B virus. Moreover, 73% (n = 87/120) of the injection providers and 90% (n = 43/48) of the waste handlers were not trained in injection safety practices and infection prevention. Qualitative data further confirmed that both providers and patients preferred injections, believing that they provide quick relief. The doctors' perceived injection use as their prescribing norm that enabled them to prove their professional credibility and to remain popular in a competitive health care market. Additionally, persistent pressure from hospital administration to use up injections before their expiry dates also influenced doctors to prescribe injections regardless of actual indications. CONCLUSIONS: As far as the patients and providers' safety is concerned, this study demonstrated a need for further research exploring the dynamics of injection use and safety in Bangladesh. In a context where a high level of injection use and unsafe practices were reported, immediate prevention initiatives need to be operated through continued intervention efforts and health providers' training in primary care hospitals in Bangladesh.

Anti-inflammatory activity of Adenanthera pavonina L., Fabaceae, in experimental animals / Atividade anti-inflamatória de Adenanthera pavonina L., Fabaceae, em animais experimentais

Adenanthera pavonina L, Fabaceae alt. Leguminosae, Bengali name 'rakta kombol', is an Indian medicinal plant. It is endemic to Southern China and India, and widely naturalized in Malaysia, Western and Eastern Africa as well as in most islands of both the Pacific and Caribbean regions. This plant has been used in traditional medicine for the treatment of asthma, boil, diarrhoea, gout, inflammations, rheumatism, tumour and ulcers, and as a tonic. The dried and ground bark of A. pavonina L. was extracted, successively, with petroleum ether (PE), dichloromethane (DCM), ethyl acetate (EtOAc) and methanol (MeOH), and the resulting extracts were assessed in vivo for anti-inflammatory activity on carrageenan-induced rat hind paw oedema as a model of inflammation. The extracts were administered orally at the doses of 200 and 400 mg/kg body weight, and statistically significant (p<0.001) anti-inflammatory effects were observed in a dose dependant manner. The MeOH extract (400 mg/kg) showed 37.10 percent (p<0.01) inhibition of inflammation at the first hour of the study and, the DCM extract (400 mg/kg) exhibited 33.11 percent (p<0.001) inhibition of inflammation at the third hour of the study which was comparable with that of reference standard drug dichlofenac sodium. The results of this study supported some of the traditional medicinal uses of this plant.

Adenanthera pavonina L, Fabaceae, conhecida na região de Bengala por "rakta kombol", é uma planta medicinal endêmica do sul da China e da Índia e amplamente difundida na Malásia, África Ocidental e Oriental, bem como na maioria das ilhas de ambas as regiões do Pacífico e Caribe. Esta planta tem sido utilizada na medicina tradicional para o tratamento da asma, febre, diarréia, gota, inflamações, reumatismo tumor, úlceras, e como tônico. Cascas secas e moídas de A. pavonina foi submetida a extração sucessiva com éter de petróleo (PE), diclorometano (DCM), acetato de etila (AcOEt) e metanol (MeOH), e os extratos foram avaliados in vivo para atividade anti-inflamatória induzida por carragenina tendo como ensaio modelo de inflamação edema de pata em ratos.. Os extratos foram administrados por via oral em doses de 200 e 400 mg/kg de peso corporal, e foram observadas efeitos anti-inflamatórios de maneira dose-dependente, estatisticamente significativos (p<0,001). O extrato metanólico (400 mg/kg) apresentou 37,10 por cento (p<0,01) de inibição da inflamação na primeira hora do estudo e, o extrato DCM (400 mg/kg) apresentou 33,11 por cento (p<0,001) na inibição da inflamação na terceira hora do estudo, que foi comparável ao resultado da substância de referência diclofenato de sódio. Os resultados deste estudo confirmaram alguns dos usos tradicionais desta planta medicinal.

Analgesic and anti-inflammatory activities of Polygonum stagninum.

The n-hexane, ethyl acetate (EtOAc), and methanol extracts of the aerial parts of Polygonum stagninum Buch.-Ham. ex Meissn. (Polygonaceae), a Bangladeshi medicinal plant, were assessed for analgesic and anti-inflammatory properties in experimental mice and/or rat models. In the acetic-acid-induced writhing test in mice, all extracts displayed a dose dependent analgesic effect. The most potent analgesic activity was observed with the EtOAc extract at the dose of 400 mg/kg body weight, with an inhibition of writhing response of 50.3% compared to 62.2% for the positive control aminopyrine. Among the extracts, n-hexane extract at the doses of 200 and 400 mg/kg body weight showed the highest levels of anti-inflammatory activity after 2 h, with the inhibition of paw edema of 60.1% and 64.1%, respectively, and this effect was much better than that of the conventional anti-inflammatory agent phenylbutazone (maximum inhibition of 38.3% after 4 h).

Analgesic and antiinflammatory activity of methanolic extract of Acalypha indica Linn.

Previous phytochemical analysis of methanolic extract of Acalypha indica L. has indicated the presence of steroid, flavonoid and terpenoid types of compounds. Since these compounds are of pharmacological interest, coupled with the use of this plant in traditional medicine, prompted us to check A. indica L. for possible analgesic and antiinflammatory activities. The methanolic extract of A. indica L. showed statistically significant (p<0.001) analgesic activity in mice in a dose-dependent manner. A sustained and significant (p<0.001) inhibition of carrageenan-induced inflammation of rat paw was observed with 125 mg/kg and 250 mg/kg body weight. The methanolic extract of A. indica L. also demonstrated antiinflammatory effect in a dose-dependent manner. Maximum inhibition by the extract was observed at 250 mg/kg body weight after three hours of ingestion, which was comparable to that of the standard drug phenylbutazone at a dose of 100 mg/kg body weight. The obtained results provide a support for the use of this plant in traditional medicine.

Analgesic and diuretic properties of alpha-santalone from Polygonum flaccidum.

Polygonum flaccidum Meissn. is an annual herb, native to Bangladesh, and well known for its analgesic, anti-inflammatory, diuretic, purgative and insecticidal properties, and also for its use against snake-bites. The analgesic and the diuretic properties of alpha-santalone (1), isolated from the aerial parts of Polygonum flaccidum, were assessed by the acetic-acid-induced writhing method and the Lipschitz test, respectively. Complete (1)H and (13)C NMR data of 1 are also presented.

Antinociceptive, anti-inflammatory and diuretic properties of Polygonum barbatum (L.) Hara var. barbata / Propriedades antinociceptiva, antiinflamatória e diurética dos extratos de P. barbatum (L.) Hara var. barbata

The antinociceptive, anti-inflammatory and diuretic properties of the extracts of P. barbatum (L.) Hara var. barbata, Polygonaceae, at the doses of 200 and 400 mg/kg body weight, were evaluated in mice/rat models using, respectively, the acetic-acid-induced writhing method, the carrageenan-induced edema test and the Lipschitz method. In the acetic-acid-induced writhing test in mice, all extracts displayed a dose dependent analgesic effect. The most potent analgesic activity was observed with the petroleum ether extract at the dose of 400 mg/kg body weight with an inhibition of writhing response 46.8 percent compared to 62.2 percent for the positive control aminopyrine. Petroleum ether extract at the dose of 400 mg/kg body weight also displayed the highest levels of anti-inflammatory activity after 2 h with the 39.3 percent inhibition of paw edema, and this effect was better than the effect observed by the conventional anti-inflammatory agent phenylbutazone (maximum inhibition of 38.3 percent after 4 h). All extracts increased urine volume in a dose-dependent manner, and the ethyl acetate extract showed a significant level of diuresis comparable to that of the standard diuretic agent furosemide.

As propriedades antinociceptiva, antiinflamatória e diurética dos extratos de P. barbatum (L.) Hara var. barbata, Polygonaceae, nas doses de 200 e 400 mg/kg de peso corpóreo foram avaliadas em modelos utilizando camundongos/ratos, respectivamente, o método de contorções induzidas por ácido acético, o teste de edema induzido por carragenina e o método de Lipschitz. No método de contorções induzidas por ácido acetic, todos os extratos apresentaram efeito nociceptivo dose dependente. O efeito nociceptivo mais potente foi observado com o extrato de éter de petróleo na dose de 400 mg/kg com uma inibição das contorções de 46,8 por cento comparado com o controle positivo de aminopirina de 62,2 por cento. O extrato de éter de petróleo na dose de 400 mg/kg também mostrou maior atividade antiinflammatoria após 2 h com 39,3 por cento de inibição do edema de pata, e este efeito foi maior que o observado para o agente antiinflamatório convencional fenilbutazona (inibição máxima de 38,4 por cento após 4 h). Todos os extratos aumentaram o volume de urina de maneira dose dependente e o extrato acetato de etila mostrou um nível de significância de diurese comparável ao agente diurético padrão, furosemida.

Total synthesis and analgesic activity of 6-fluoroindan-1-acetic acid and its 3-oxo derivative.

6-Fluoro-3-oxo-indan-1-acetic acid (5) and 6-fluoroindan-1-acetic acid (6) were conveniently synthesised from 3-fluorobenzaldehyde in four and five steps, respectively. The structures of these new compounds and two other intermediates, 3-fluorobenzylidine-bis-acetoacetate (2) and 3-fluoro-beta-phenyl glutaric acid (3) were elucidated by spectroscopic means, notably, HRMS, 1D and 2D NMR. The analgesic activity of compounds 5 and 6 were assessed by the acetic acid induced writhing in Swiss albino mice.

Anti-inflammatory activity of indanyltetrazole derivatives.

A number of indanyl tetrazolederivatives namely 5-(6'-chloroindan-1'-yl)tetrazole (CIT), 5-(6'-bromoindan-1'-yl)tetrazole (BIT), 5-(6'-chloroindan-1'-yl)methyltetrazole (CIMT), 5-(6'-bromoindan-1'-yl)methyl-tetrazole (BIMT) were evaluated for the anti-inflammatory activity in carragennan induced rat paw edema in Swiss albino Wister rats for 24-hour period at the dose of 100 mg/kg of body weight by intraperitoneal route where phenylbutazone (PBZ) was used as the standard. All of these compounds exhibited inhibition on rat paw edema with peak actions observed following 3 hours after administration. Moreover, compounds CIMT and BIMT were further evaluated at dose of 50 mg/kg of body weight. Among the compounds, CIMT showed higher activity than others and was very close to standard phenylbutazone.

Anti-inflammatory and analgesic effects of Hedychium coronarium Koen.

Successive hexane, chloroform and methanol extracts of the rhizome of Hedychium coronarium Koen. (HC) were subjected to evaluate analgesic and anti-inflammatory activities in animal model. In acetic acid-induced writhing test, the chloroform and methanol extract at doses of 400 mg/kg body weight elicited 27.23 and 40.59% inhibition of writhing reflex respectively. Both the chloroform and methanol extracts showed significant elongation of tail flick time (41.15 and 61.32% elongation respectively) at 400 mg/kg body weight. In carrageenan induced rat paw edema test, the chloroform and methanol extracts at a dose of 400 mg/kg body weight showed statistically significant (P<0.01) inhibition of paw edema by 27.46 and 32.48%, respectively at the third hour after carrageenan injection.