RETRACTED: Agrawal et al. Artemisia Extracts and Artemisinin-Based Antimalarials for COVID-19 Management: Could These Be Effective Antivirals for COVID-19 Treatment? Molecules 2022, 27, 3828.

The journal retracts the article "Artemisia Extracts and Artemisinin-Based Antimalarials for COVID-19 Management: Could These Be Effective Antivirals for COVID-19 Treatment [...].

Natural Alkaloids as Multi-Target Compounds towards Factors Implicated in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia in elderly people; currently, there is no efficient treatment. Considering the increase in life expectancy worldwide AD rates are predicted to increase enormously, and thus the search for new AD drugs is urgently needed. A great amount of experimental and clinical evidence indicated that AD is a complex disorder characterized by widespread neurodegeneration of the CNS, with major involvement of the cholinergic system, causing progressive cognitive decline and dementia. The current treatment, based on the cholinergic hypothesis, is only symptomatic and mainly involves the restoration of acetylcholine (ACh) levels through the inhibition of acetylcholinesterase (AChE). Since the introduction of the Amaryllidaceae alkaloid galanthamine as an antidementia drug in 2001, alkaloids have been one of the most attractive groups for searching for new AD drugs. The present review aims to comprehensively summarize alkaloids of various origins as multi-target compounds for AD. From this point of view, the most promising compounds seem to be the ß-carboline alkaloid harmine and several isoquinoline alkaloids since they can simultaneously inhibit several key enzymes of AD's pathophysiology. However, this topic remains open for further research on detailed mechanisms of action and the synthesis of potentially better semi-synthetic analogues.

Artemisia Extracts and Artemisinin-Based Antimalarials for COVID-19 Management: Could These Be Effective Antivirals for COVID-19 Treatment?

As the world desperately searches for ways to treat the coronavirus disease 2019 (COVID-19) pandemic, a growing number of people are turning to herbal remedies. The Artemisia species, such as A. annua and A. afra, in particular, exhibit positive effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and COVID-19 related symptoms. A. annua is a source of artemisinin, which is active against malaria, and also exhibits potential for other diseases. This has increased interest in artemisinin's potential for drug repurposing. Artemisinin-based combination therapies, so-called ACTs, have already been recognized as first-line treatments against malaria. Artemisia extract, as well as ACTs, have demonstrated inhibition of SARS-CoV-2. Artemisinin and its derivatives have also shown anti-inflammatory effects, including inhibition of interleukin-6 (IL-6) that plays a key role in the development of severe COVID-19. There is now sufficient evidence in the literature to suggest the effectiveness of Artemisia, its constituents and/or artemisinin derivatives, to fight against the SARS-CoV-2 infection by inhibiting its invasion, and replication, as well as reducing oxidative stress and inflammation, and mitigating lung damage.

Recent Progress on Biological Activity of Amaryllidaceae and Further Isoquinoline Alkaloids in Connection with Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease recognized as the most common form of dementia among elderly people. Due to the fact that the exact pathogenesis of AD still remains to be fully elucidated, the treatment is only symptomatic and available drugs are not able to modify AD progression. Considering the increase in life expectancy worldwide, AD rates are predicted to increase enormously, and thus the search for new AD drugs is urgently needed. Due to their complex nitrogen-containing structures, alkaloids are considered to be promising candidates for use in the treatment of AD. Since the introduction of galanthamine as an antidementia drug in 2001, Amaryllidaceae alkaloids (AAs) and further isoquinoline alkaloids (IAs) have been one of the most studied groups of alkaloids. In the last few years, several compounds of new structure types have been isolated and evaluated for their biological activity connected with AD. The present review aims to comprehensively summarize recent progress on AAs and IAs since 2010 up to June 2021 as potential drugs for the treatment of AD.

Chemical and Biological Aspects of Montanine-Type Alkaloids Isolated from Plants of the Amaryllidaceae Family.

Plants of the Amaryllidaceae family are promising therapeutic tools for human diseases and have been used as alternative medicines. The specific secondary metabolites of this plant family, called Amaryllidaceae alkaloids (AA), have attracted considerable attention due to their interesting pharmacological activities. One of them, galantamine, is already used in the therapy of Alzheimer's disease as a long acting, selective, reversible inhibitor of acetylcholinesterase. One group of AA is the montanine-type, such as montanine, pancracine and others, which share a 5,11-methanomorphanthridine core. So far, only 14 montanine-type alkaloids have been isolated. Compared with other structural-types of AA, montanine-type alkaloids are predominantly present in plants in low concentrations, but some of them display promising biological properties, especially in vitro cytotoxic activity against different cancerous cell lines. The present review aims to summarize comprehensively the research that has been published on the Amaryllidaceae alkaloids of montanine-type.

The Genus Nerine Herb. (Amaryllidaceae): Ethnobotany, Phytochemistry, and Biological Activity.

Nerine Herbert, family Amaryllidaceae, is a genus of about 30 species that are native to South Africa, Botswana, Lesotho, Namibia, and Swatini (formerly known as Swaziland). Species of Nerine are autumn-flowering, perennial, bulbous plants, which inhabit areas with summer rainfall and cool, dry winters. Most Nerine species have been cultivated for their elegant flowers, presenting a source of innumerable horticultural hybrids. For many years, species of Nerine have been subjected to extensive phytochemical and pharmacological investigations, which resulted in either the isolation or identification of more than fifty Amaryllidaceae alkaloids belonging to different structural types. Amaryllidaceae alkaloids are frequently studied for their interesting biological properties, including antiviral, antibacterial, antitumor, antifungal, antimalarial, analgesic, cytotoxic, and cholinesterase inhibition activities. The present review aims to summarize comprehensively the research that has been reported on the phytochemistry and pharmacology of the genus Nerine.

Effect of aqueous extract and anthocyanins of calyces of Hibiscus sabdariffa (Malvaceae) in rats with adenine-induced chronic kidney disease.

OBJECTIVES: The aim of this work was to assess the possible beneficial effects of aqueous extracts of Hibiscus sabdariffa L. calyces and anthocyanins isolated therefrom in an adenine-induced chronic kidney disease (CKD) model. METHODS: Rats were orally given, for 28 consecutive days, either adenine alone or together with either aqueous extract of H. sabdariffa calyces (5 and 10%) or anthocyanins (50, 100 and 200 mg/kg of anthocyanin concentrate). For comparative purposes, two groups of rats were given lisinopril (10 mg/kg). KEY FINDINGS: When either H. sabdariffa aqueous extract or the anthocyanins isolated from it was administered along with adenine, the adverse effects of adenine-induced CKD were significantly lessened, mostly in a dose-dependent manner. The positive effects were similar to those obtained by administration of lisinopril. CONCLUSIONS: The results obtained show that both H. sabdariffa and its anthocyanins could be considered as possible promising safe dietary agents that could be used to attenuate the progression of human CKD. This could have added significance as H. sabdariffa tea is widely consumed in many parts of Africa and Asia and is thus readily available.

Anthocyanins of Hibiscus sabdiffera calyces from Sudan.

Extracts of the calyces of Hibiscus sabdariffa are widely used in folk medicine to combat many illnesses. The active constituents of the extracts have been shown on several occasions to be anthocyanins. In our current studies the biological activities of an extract of H. sabdariffa calyces purchased in Oman, but grown in Sudan, are being compared with those of the anthocyanins isolated from them, and, for this, the anthocyanin profile of the extract needed to be ascertained. Although several anthocyanins were detected by UHPLC-ESI-MS/MS, delphinidin-3-sambubioside (major) and cyanidin-3-sambubioside were predominant.

Assessment of dual life stage antiplasmodial activity of british seaweeds.

Terrestrial plants have proven to be a prolific producer of clinically effective antimalarial drugs, but the antimalarial potential of seaweeds has been little explored. The main aim of this study was to assess the in vitro chemotherapeutical and prophylactic potential of the extracts of twenty-three seaweeds collected from the south coast of England against blood stage (BS) and liver stage (LS) Plasmodium parasites. The majority (14) of the extracts were active against BS of P. falciparum, with brown seaweeds Cystoseira tamariscifolia, C. baccata and the green seaweed Ulva lactuca being the most active (IC(50)s around 3 µg/mL). The extracts generally had high selectivity indices (>10). Eight seaweed extracts inhibited the growth of LS parasites of P. berghei without any obvious effect on the viability of the human hepatoma (Huh7) cells, and the highest potential was exerted by U. lactuca and red seaweeds Ceramium virgatum and Halopitys incurvus (IC50 values 14.9 to 28.8 µg/mL). The LS-active extracts inhibited one or more key enzymes of the malarial type-II fatty acid biosynthesis (FAS-II) pathway, a drug target specific for LS. Except for the red seaweed Halopitys incurvus, all LS-active extracts showed dual activity versus both malarial intracellular stage parasites. This is the first report of LS antiplasmodial activity and dual stage inhibitory potential of seaweeds.

Headspace, solid-phase micro-extraction, gas chromatographic-mass spectrometric analysis of terpenoids in the latex of Euphorbia species.

The volatile and semi-volatile terpenoids in the latex of Euphorbia amygdaloides, E. exigua, E. helioscopia, and E. peplus were analyzed by headspace, solid-phase micro-extraction (HS-SPME), coupled with gas chromatography-mass spectrometry. The volatiles were extracted using a 100 microm polydimethylsiloxane SPME fiber under optimized extraction conditions. The compounds detected encompassed a range of chemical classes, but only terpenoids were evaluated. Only sesquiterpene hydrocarbons were detected in the tested samples of E. exigua, E. helioscopia, and E. peplus, with beta-caryophyllene being the major one, but were never recorded in latex samples of E. amygdaloides, in which only the diterpene hydrocarbon kaur-16-ene was detected. Alpha-Humulene was consistently found in samples of E. helioscopia, and E. peplus, but never in those of the other two species. These preliminary results show that the developed procedure is suitable for the analysis of small samples of Euphorbia latex and that, for each individual species, there is very little qualitative difference between samples, regardless of either place or date of collection.

Trigonelline and other betaines in species of Laminariales.

A collection of Laminariales species was made with examples in each of the presently recognized families of the order. Extracts of each species were examined for betaines, using primarily 'H NMR spectroscopy for their identification. Glycinebetaine was detected in all species tested and would appear to be a consistent feature of the Laminariales. Gamma-Aminobutyric acid betaine was found in all species of Laminaria examined and in three of the five Saccharina species (family Laminariaceae), but was not detected in species of either other genera of the family or in those of other Laminariales families. Trigonelline was found in some Laminaria and Saccharina species, as well as in the north Pacific species Postelsia palmaeformis (Laminariaceae), Pseudochorda nagaii (Pseudochordaceae) and Akkesiphycus lubricus (Akkesiphycaceae).

Long-term ingestion of Hibiscus sabdariffa calyx extract enhances myocardial capillarization in the spontaneously hypertensive rat.

The effects of Hibiscus sabdariffa (HS) in lowering blood pressure in human and animal hypertension have been documented. This study investigated the effect of the water extract of the dried calyx of HS and Hibiscus anthocyanins (HAs) on left ventricular myocardial capillary length and surface area in spontaneously hypertensive rats (SHRs). Twelve-week-old male SHRs were divided into eight groups (six rats in each group). Three groups were given three doses; 10%, 15% and 20% of the water extract of HS in lieu of drinking water for 10 consecutive weeks (HS10, HS15 and HS20) with one group kept as control (C). Another three groups were given three doses of the HAs orally at doses of 50, 100 and 200 mg/kg for five consecutive days with one group kept as a control (C). Systolic (SBP) and diastolic (DBP) blood pressures, as well as heart rate (HR), were measured weekly. After the experimental protocols, the left ventricles (LV) of all rats were obtained. Capillary surface area density and length density were determined by unbiased sterological methods on 3 µm LV tissue samples from perfusion-fixed hearts. HS ingestion significantly reduced SBP, DBP and LV mass in a dose-dependent fashion but did not affect the HR. HS significantly increased surface area and length density of myocardial capillaries by 59%, 65% and 86%, and length density by 57%, 77% and 57%, respectively. Myocyte nuclear volume was significantly decreased in HS-treated rats. There was a decrease (although insignificant) in SBP and DBP with HA ingestion compared with controls. These changes suggest that the observed beneficial effect of HS on high BP in SHRs could be mediated through a reduction in the diffusion distance between capillaries and myocytes, as well as new vessel formation. It is proposed that these effects might be beneficial in restoring myocyte normal nutritional status compromised by the hypertrophic state of hypertension.

Effect of Hibiscus sabdariffa and its anthocyanins on some reproductive aspects in rats.

An aqueous extract of Hibiscus sabdariffa L. is a common beverage in many parts of the world. Reports on its effect on reproduction are conflicting, with anecdotal evidence that the plant is an aphrodisiac, while others report that it is estrogenic, and adversely affects spermatogenesis in rats. We have studied the effect of different concentrations of aqueous extracts of H. sabdariffa calyces (10%, 15% and 20%) used as drinking water for 10 consecutive weeks, and its anthocyanins (50, 100, 200 mg/kg for 5 days, orally) on the weight and histology of the testis, and on some biochemical constituents in testicular homogenates, in addition to the plasma concentrations of testosterone, luteinizing hormone and estradiol. The possible presence of an estrogenic effect of the extract and anthocyanins on the uteri of immature female rats was also tested. Neither the H. sabdariffa extract nor the anthocyanins significantly altered either testicular weight and histology, or uterus weight. Plasma concentrations of the three hormones studied, the testicular concentrations of protein, reduced glutathione and total cholesterol, and superoxide dismutase activity were all insignificantly affected by either the extract or the anthocyanins, except for a slight, but statistically significant, decrease in testicular protein concentration caused by the 15% aqueous extract when compared with controls. These results suggest that H. sabdariffa exerts no adverse effect on the male reproductive system. Consumption of H. sabdariffa aqueous extract inhibited the growth of the rats compared with the controls.

Bioactivity-guided study of antiproliferative activities of Salvia extracts.

The cytotoxic activities of the n-hexane, chloroform and aqueous methanolic fractions prepared from the methanolic extract of the leaves of 23 Salvia taxa were studied for their cell growth-inhibitory activity against human cervix adenocarcinoma (HeLa), skin carcinoma (A431) and breast adenocarcinoma (MCF7) cells using the MTT assay. The n-hexane fractions of six Salvia taxa (S. hispanica, S. nemorosa, S. nemorosa 1. albiflora, S. pratensis, S. recognita and S. ringens) and the chloroform fraction ofS. officinalis 1. albiflora produced over 50% growth inhibition of the skin carcinoma cell line. None of the tested extracts showed substantial (above 50%) antiproliferative effects against HeLa and MCF7 cells. S. ringens was the most powerful among the studied Salvia species with a 61.8% cell growth inhibitory activity on A431 cells. In the case of S. ringens, other plant parts were also tested for antiproliferative effect, and the highest activities were recorded for the root extract. This was subjected to bioactivity-guided fractionation, which yielded four abietane diterpenes (royleanone, horminone, 7-O-methyl-horminone and 7-acetyl-horminone), one triterpene (erythrodiol-3-acetate) and beta-sitosterol. Horminone, 7-acetyl-horminone and erythrodiol-3-acetate displayed marked concentration-dependent antiproliferative effects, while royleanone and 7-O-methyl-horminone produced weaker activities.

Antiprotozoal, antitubercular and cytotoxic potential of cyanobacterial (blue-green algal) extracts from Ireland.

Cyanobacteria (= blue-green algae) are prolific producers of structurally distinct and biologically active metabolites. In the continuation of our search for new sources of anti-infective natural products, we have assessed the in vitro antiprotozoal (Plasmodium falciparum, Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani) and antitubercular (Mycobacterium tuberculosis) potential of samples of two terrestrial cyanobacteria, Nostoc commune (collected when desiccated and wet) and Rivularia biasolettiana. The cytotoxic potential of the extracts was also evaluated against primary L6 cells. Except for T. cruzi and M. tuberculosis, the crude extracts were active against all the organisms tested and showed no toxicity. The crude extracts were then partitioned between n-hexane, chloroform and aqueous methanol and retested against the same panel of pathogens. The chloroform sub-extracts of both N. commune samples showed significant activity against T. b. rhodesiense (IC50 values 2.0 and 3.5 microg/mL) and P. falciparum (IC50s 7.4 and 5.8 microg/mL), with low toxicity. This trend was also true for R. biasolettiana extracts, and its chloroform sub-extract showed notable activity against all parasitic protozoa. There were differences in the biological activity profiles of extracts derived from desiccated and hydrated forms of N. commune. To our knowledge, this is the first study assessing the anti-infective activity of desiccated and hydrated forms of N. commune, as well as R. biasolettiana. Furthermore, the present work reports such biological activity in terrestrial cyanobacteria from Ireland for the first time. These results warrant the further study of Irish terrestrial cyanobacteria as a valuable source of new natural product leads for the treatment of parasitic protozoal infections.

Experimental gentamicin nephrotoxicity and agents that modify it: a mini-review of recent research.

The aminoglycoside antibiotic gentamicin (GM) is still widely used against infections by Gram-positive and Gram-negative aerobic bacteria. Its therapeutic efficacy, however, is limited by renal impairment that occurs in up to 30% of treated patients. The drug may accumulate in epithelial tubular cells causing a range of effects starting with loss of the brush border in epithelial cells and ending in overt tubular necrosis, activation of apoptosis and massive proteolysis. GM also causes cell death by generation of free radicals, phospholipidosis, extracellular calcium-sensing receptor stimulation and energetic catastrophe, reduced renal blood flow and inflammation. Many drugs have been shown to either ameliorate or potentiate GM nephrotoxicity. This article aims at updating the literature that has been published in the past decade on the effects of agents that either ameliorate or augment the nephrotoxicity of this aminoglycoside. Notable among the new ameliorating procedures are gene therapy, such as intravenous cell therapy with serum amyloid A protein-programmed cells, and the use of some novel antioxidant agents and oils of natural origin. These include, for example, green tea, garlic saffron, grape seed extracts as well as sesame and oleanolic oils. Agents that may augment GM nephrotoxicity include indomethacin, cyclosporin, uric acid and the Ca(++) -channel blocker verapamil. Most of the nephroprotective agents mentioned here have not been tested in large controlled clinical trials. Because of their relative safety and effectiveness, antioxidant agents seem to be good candidates for testing in humans.

Stable molluscicide formulation of an aqueous extract of Euphorbia myrsinites.

Aqueous extracts of Euphorbia myrsinites L. (Euphorbiaceae) were tested for molluscicidal activity against Biomphalaria glabrata; LC50 values of 15.1 and 8.9 ppm were obtained for the stem and leaf extracts, respectively, which are within the WHO limit for an effective molluscicide. However, the extracts were found to be unstable at room temperature and the level of activity fell rapidly (about 50% after 7 days at 20 °C). Moreover, the extracts were shown to be cytotoxic and would thus, if used as a molluscicide, be potentially hazardous to the user. As a result, attempts were made to produce a simple formulation that was stable and easy to handle, thereby reducing the danger to the user, but which would decompose rapidly in aqueous solution after application, thus reducing any lasting ecological damage. A product based on spray drying the aqueous extract of the leaves and stems led to a preparation that, although slightly lower in activity than the original extract, was stable at room temperature for at least a year, but which decomposed in aqueous solution at a similar rate to the original extract.

Antimycobacterial, antiprotozoal and cytotoxic potential of twenty-one brown algae (Phaeophyceae) from British and Irish waters.

In the continuation of our research on seaweeds, crude extracts of 21 brown algae collected from the south coast of England and the west coast of Ireland were screened for in vitro trypanocidal, leishmanicidal and antimycobacterial activities. Mammalian stages of a small set of parasitic protozoa; i.e. Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, and the tubercle bacillus Mycobacterium tuberculosis were used as test organisms. The extracts were also evaluated for selectivity by testing on a mammalian cell line (L6 cells). Only four extracts were moderately active against T. cruzi, whereas all algal extracts showed significant activity against T. brucei rhodesiense, with Halidrys siliquosa and Bifurcaria bifurcata (Sargassaceae) being the most potent (IC50 values 1.2 and 1.9 µg/mL). All algal extracts also displayed leishmanicidal activity, with H. siliquosa and B. bifurcata again being the most active (IC50s 6.4 and 8.6 µg/mL). When tested against M. tuberculosis, only the B. bifurcata extract was found to have some antitubercular potential (MIC value 64.0 µg/mL). Only three seaweed extracts, i.e. H. siliquosa, B. bifurcata and Cystoseira tamariscifolia showed some cytotoxicity. To our knowledge, this is the first study on the antiprotozoal and antimycobacterial activity of brown algae from British and Irish waters.

Betaine yields from marine algal species utilized in the preparation of seaweed extracts used in agriculture.

Ascophyllum nodosum, and to a lesser extent, Laminaria digitata, L. hyperborea and Fucus serratus, are marine algal species utilized in the commercial production of seaweed extracts used in agriculture. Betaines have been shown to be important constituents of these extracts, but there appears to have been no study made on whether there are variations in the betaine contents of these species based on either the place or date of collection. Samples of each of the four species were collected from widely separated areas at different times of the year. Also, in the case of A. nodosum, approximately monthly collections were made from one location. The betaines detected in the various collections of the same species showed little variation, although in the case ofA. nodosum, glycinebetaine was found as a minor constituent in some samples, but was not detected in others. Trigonelline was found in all the tested samples of the two Laminaria species; this is, to our knowledge, the first record of this betaine in marine algae. With the exception of trigonelline in the Laminaria species, the betaine yields from the various samples of L. digitata, L. hyperborea and F. serratus showed little variation, regardless of either the place or date of collection. The trigonelline contents of the Laminaria species collected at one location (Finavarra, Ireland), in particular of L. hyperborea, was substantially greater than those from the other places of collection. In the case of A. nodosum, the betaine yields from samples collected at one site (Dale, Pembrokeshire, UK) were significantly higher than those from the other places of collection, which were very similar to each other. There was no clear indication of seasonal variation in betaine yields from A. nodosum.

Antiprotozoal, antimycobacterial and cytotoxic potential of twenty-three British and Irish red algae.

As part of our continuing research on seaweeds, we have screened the crude extracts of 23 red marine algae collected from England and Ireland. The clinically important blood-stage life forms of Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani and Mycobacterium tuberculosis were used as test organisms in the in vitro assays. The selectivity of the extracts was determined by using mammalian skeletal myoblast (L6) cells. All algal extracts showed activity against T. brucei rhodesiense, with Corallina officinalis and Ceramium virgatum being the most potent (IC(50) values 4.8 and 5.4 microg/ml), whilst none of the algal extracts inhibited the growth of T. cruzi. Except for Porphyra leucosticta, extracts from all seaweeds also showed leishmanicidal activity with IC(50) values ranging from 16.5 to 85.6 microg/ml. Only the crude extract of Calliblepharis jubata showed some weak activity against Mycobacterium tuberculosis (MIC value 256 microg/ml), while the others were inactive at this concentration. Corallina officinalis was the only seaweed that displayed some marginal cytotoxicity (IC(50) value 88.6 microg/ml), and all remaining extracts were non-toxic towards L6 cells at 90 microg/ml concentration. To our knowledge, this is the first study reporting antiprotozoal and antimycobacterial activity of British and Irish red algae.