Cinchona Calisaya Research Articles

Cinchonine: A Versatile Pharmacological Agent Derived from Natural Cinchona Alkaloids.

Cinchonine is one of the Cinchona alkaloids that is commercially extracted from the Peruvian bark of Cinchona officinalis L. (Family: Rubiaceae). It is also obtained in much lower quantities from other species of Cinchona, such as Cinchona calisaya, Cinchona succirubra, and Cinchona pubescens, and in some other plants, such as Remijia peruviana. Cinchonine has been historically used as an anti-malarial agent. It also has a wide range of other biological properties, including anti-cancer, anti-obesity, anti-inflammatory, anti-parasitic, antimicrobial, anti-platelet aggregation, and anti-osteoclast differentiation. This review discusses the pharmacological activity of cinchonine under different experimental conditions, including in silico, in vitro, and in vivo. It also covers the compound's physicochemical properties, toxicological aspects, and pharmacokinetics. A comprehensive literature search was conducted on multiple online databases, such as PubMed, Scopus, and Google Scholar. The aim was to retrieve a wide range of review/research papers and bibliographic sources. The process involved applying exclusion and inclusion criteria to ensure the selection of relevant and high-quality papers. Cinchonine has numerous pharmacological properties, making it a promising compound for various therapeutic applications. It induces anti-cancer activity by activating caspase-3 and PARP-1, and triggers the endoplasmic reticulum stress response. It up-regulates GRP78 and promotes the phosphorylation of PERK and ETIF-2α. Cinchonine also inhibits osteoclastogenesis, inhibiting TAK1 activation and suppressing NFATc1 expression by regulating AP-1 and NF-κB. Its potential anti-inflammatory effects reduce the impact of high-fat diets, making it suitable for targeting obesity-related diseases. However, research on cinchonine is limited, and further studies are needed to fully understand its therapeutic potential. Further investigation is needed to ensure its safety and efficacy in clinical applications. Overall, this review article explains the pharmacological activity of cinchonine, its synthesis, and physicochemical properties, toxicological aspects, and pharmacokinetics.

A Review: Pharmacological Activities of Quinoline Alkaloid of Cinchona sp.

Cinchona is a plant used in traditional malaria treatment. This review aims to examine pharmacological activities to increase the benefits and uses of the bioactive compounds found in the bark of the Cinchona trees as medicine and cosmetics. A literature search was conducted through the internet database https://pubmed.ncbi.nlm.nih.gov/; https://scholar.google.com/; https://www.sciencedirect.com/; https://www.wiley.com/en-us from 1998-2022. The main phytochemical content of Cinchona bark is quinoline alkaloids (quinine, cinchonidine, cinchonine, and cinchonidine), with total alkaloid concentrations varying between 6 and 15% (Cinchona succirubra ranging from 5-7%, Cinchona calisaya 4-7% and Cinchona ledgeriana 5-14%). Cinchona quinoline alkaloids have the same active site on the nitrogen atom in the quinuclidine ring and the methylene alcohol functional group, which plays an essential role in their pharmacological activity. Besides being used as an antimalarial, Cinchona alkaloids are currently being developed as their anticancer, antioxidant, antidiabetic, antifungal, muscle cramps, hair growth stimulant, antimicrobial, antiobesity, antiplatelet, antiviral, anesthetic, and antipyretic properties. Conclusion: Quinoline alkaloids of Cinchona sp have various pharmacological activities that have the potency to be developed as drugs and cosmetics.

Genetic profiles of three Cinchona species in Junghuhn Natural Reserve, Indonesia

Cinchona species were widely used as ancient medicines for different diseases because they contain the active component quinine and its derivatives. However, studies on the molecular aspects of cinchona, including its genetic diversity, have not been reported because most previous works focused on the administration of the antimalarial cinchona alkaloid. Quinine is also being tested as alternative compound for the treatment of Covid-19. The Junghuhn Natural Reserve in Indonesia contains three different types of cinchona plants, namely, Cinchona calisaya, Cinchona pubescens, and Cinchona sp. Given that the genetic diversity and kinship of these species have never been studied, collecting data on the cinchona gene pool has become imperative. This study analyzed the genetic diversity of the cinchona species in the Junghuhn Natural Reserve, Indonesia, by using eight RAPD markers, i.e., OPA-2, OPA-9, OPB-02, OPB-03, OPB-04, OPB-05, OPB-7, and OPJ-07, during 2020 at the University of Jenderal Soedirman, Purwokerto-Indonesia. Polymorphic band data were obtained. Then, phenogram analysis was conducted by using UPGMA and maximum parsimony with MEGA7. The RAPD profiles of Cinchona species (C. calisaya, C. pubescent, and Cinchona sp.) revealed polymorphism with different markers, i.e., OPA-2 (90%), OPB-2 (75%), OPB-5 (75%), OPB-3 (66.66%), OPB-4 (66.66%), OPB-7 (66.66%), OPJ-7 (66.66%), and OPA-9 (58.33%) sequentially with total polymorphism (70.62%). C. calisaya was identified as the most distinctive species. UPGMA yielded a coefficient of 0.200 and two distinctive groups: Group I, which comprised C. pubescens and Cinchona sp. with the p-distance value of 0.333, and Group II, which contained C. calisaya. Ixora sp. was treated as an outgroup plant. The topology of the dendrogram was consistent with that of the UPGMA dendrogram. Results may be used for the further exploration of the genetic diversity of cinchona species.

Antiviral and Immunity-modulating Natural Herbs in the Prevention of COVID-19

The COVID-19 has spread all over the world and there is no single drug or medicine for the prevention and the treatment of this deadly disease. One can get prevention from this disease by boosting the immune system. Persons with weak immune system e.g. children, elder patients or patients with preexisting diseases affect rapidly due to coronavirus. This novel coronavirus attacks mainly on the person immunity. For the centuries the herbal medicinal plants have many beneficial effects against deadly viruses. Herbal medicines provide a rich resource for new antiviral drug development. These natural agents interact with the life cycle of virus such as virus entry, replication, assembly and release. In this review, the importance, immunomodulator, antiviral and pharmacological activities of some medicinal plants, namely, Allium Sativum, Zingiber Officinalis, Cinnamomum zeylanicum, Curcuma longa, Ocimum sanctum, Glycyrrhiza glabra, Ginseng, Black pepper, Emblica officinalis, Withania somnifera, Tinospora cordifolia, Echinacea purpurea, Azadirachta indica, Piper betel, Eugenia caryophyllata, Cinchona calisaya, Nigella sativa, Cuminum cyminum are highlighted. These medicinal plants have many phytoconstituents like alkaloids, glycosides, terpenoids, flavonoids, lactones, polysaccharides, volatile oils, tannins, resins, etc which are helpful for boosting immunity and will help in the prevention and in the management of COVID-19. Several types of research attempted to use herbal medicines against COVID-19.

Effect of Medium pH and Light on Quinidine Production in Cinchona calisaya Wedd. Endophytic Fungi

Quinidine has pharmaceutical importance as an antimalarial, antiarrhythmia, antimicrobial, anticancer, antioxidant, astringent, and bitter flavoring agent. Quinidine is in high demand, yet its production from the bark of the quina tree (Cinchona calisaya) is limited. Quinidine production from quina tree fungal endophytes, namely Aspergillus sydowii, Diaporthe sp., Diaporthe lithicola, Fusarium oxysporum, and F. solani is lower than the quinidine content of the tree bark. This study attempted to increase quinidine production from these fungi. This research aimed to determine the optimum culture conditions for quinidine production from endophytic fungi. Quinidine was produced by in vitro culturing of the fungal endophytes in potato dextrose broth (PDB) medium under different culture conditions, i.e., a combination of an initial medium pH of 6.2 or 6.8, with or without light, in a static condition for 21 days of incubation at room temperature. Production under natural daylight in PDB medium without pH modification was used as the control. At the end of the incubation period, the mycelial mass was separated from the filtrate. The dried biomass and chloroform-extracted filtrate were weighed. Quinidine in the extract was analyzed qualitatively and quantitatively using high-performance liquid chromatograph. Quinidine production was affected by both light and the initial pH of the medium, depending on the fungal strain used. A significant increment in quinidine production, approximately 1.1-9.3-fold relative to its respective control was obtained from all fungi under their optimum conditions. Quinidine production in most of the fungi was significantly correlated with their biomass production but not with their extract production. Of those five fungi, F. solani that was cultured in PDB medium with an initial pH of 6.2 and incubated under continuous light produced the highest concentration of quinidine with low biomass. The quinidine production of all fungal endophytes studied was affected by the culture conditions. F. solani is the most promising fungus for use as a quinidine production agent.

Phylogeny Predicts the Quantity of Antimalarial Alkaloids within the Iconic Yellow Cinchona Bark (Rubiaceae: Cinchona calisaya).

Considerable inter- and intraspecific variation with respect to the quantity and composition of plant natural products exists. The processes that drive this variation remain largely unknown. Understanding which factors determine chemical diversity has the potential to shed light on plant defenses against herbivores and diseases and accelerate drug discovery. For centuries, Cinchona alkaloids were the primary treatment of malaria. Using Cinchona calisaya as a model, we generated genetic profiles of leaf samples from four plastid (trnL-F, matK, rps16, and ndhF) and one nuclear (ITS) DNA regions from twenty-two C. calisaya stands sampled in the Yungas region of Bolivia. Climatic and soil parameters were characterized and bark samples were analyzed for content of the four major alkaloids using HPLC-UV to explore the utility of evolutionary history (phylogeny) in determining variation within species of these compounds under natural conditions. A significant phylogenetic signal was found for the content of two out of four major Cinchona alkaloids (quinine and cinchonidine) and their total content. Climatic parameters, primarily driven by changing altitude, predicted 20.2% of the overall alkaloid variation, and geographical separation accounted for a further 9.7%. A clade of high alkaloid producing trees was identified that spanned a narrow range of altitudes, from 1,100 to 1,350 m. However, climate expressed by altitude was not a significant driver when accounting for phylogeny, suggesting that the chemical diversity is primarily driven by phylogeny. Comparisons of the relative effects of both environmental and genetic variability in determining plant chemical diversity have scarcely been performed at the genotypic level. In this study we demonstrate there is an essential need to do so if the extensive genotypic variation in plant biochemistry is to be fully understood.

Unexpectedly High Beta-Diversity of Root-Associated Fungal Communities in the Bolivian Andes.

Bolivia is one of the most biologically diverse countries on the planet. Between the Andes and the Amazon drainage basin spans the Yungas, a vast forested region shown to be extremely species rich in macro-organisms. However, it remains unclear whether this high diversity is also reflected in microbial diversity. Here we assess the genetic, taxonomic and functional diversity of root-associated fungi surrounding Cinchona calisaya trees, a typical element of the intermediate altitudes of the Bolivian Yungas. We determine the relative effects of edaphic properties, climate, and geography in regulating fungal community assembly. We show that α-diversity for these fungal communities was similar to temperate and arid ecosystems, averaging 90.1 operational taxonomic units (OTUs) per sample, with reads predominantly assigned to the Ascomycota phylum and with a saprotrophic lifestyle. ß-diversity was calculated as the distance-decay rate, and in contrast to α-diversity, was exceptionally high with a rate of −0.407. Soil properties (pH and P) principally regulated fungal community assembly in an analogous manner to temperate environments, with pH and phosphorus explaining 7.8 and 7.2% of community variation respectively. Surprisingly, altitude does not influence community formation, and there is limited evidence that climate (precipitation and temperature) play a role. Our results suggest that sampling should be performed over a wide geographical and environmental range in order to capture the full root-associated fungal diversity in subtropical regions. This study sheds further light on the diversity and distribution of the world's “hidden biodiversity.”

Reproductive toxicology and clastogenic evaluation in mice of a phytotherapeutic formulation obtained from Cinchona calisaya Weddel (Rubiaceae) used in Brazilian folk medicine as female fertility stimulant

Ethnopharmacological relevanceIn Brazil, a phytotherapeutic preparation produced from a standardized tincture of Cinchona calisaya Weddel such that each mL of product contains 400µg of quinine, known in Portuguese as Água Inglesa® (English water), is indicated by the manufacturer as a tonic, appetite stimulant, and digestive. However, this preparation has long been used in folk medicine as a female fertility stimulant. Despite its widespread use in folk medicine to stimulate female fertility, no study has been undertaken to assess the potential teratogenic and genotoxic effects of this phytotherapeutic preparation. The aim of the present study was to investigate possible toxic reproductive effects in mice caused by exposure to Água Inglesa®, either before mating or during the pre- and post-embryo implantation periods. The genotoxic potential was evaluated using the micronucleus assay. Material, Methods, and ResultsVirgin female mice, with at least one estrous cycle evidenced by vaginal cytology, were divided into five groups of 15 individuals each (Group I – control, Group II – treated with ethanol solution at 16%, Groups III, IV and V treated with phytotherapeutic preparation at 1.5mL/kg/day, 3.0mL/kg/day and 4.5mL/kg/day, respectively). After the first 28 days of treatment, females were caged individually with adult fertile males. Pregnant females continued to receive treatment for seven days (preimplantation period). Body weight was recorded weekly during treatment. Signs of toxicity (weight loss, food intake, piloerection, apathy, prostration, diarrhea, seizures, behavioral changes, and locomotion) were also observed. The females were sacrificed on the 15th day of pregnancy, uterine horns were evaluated for implantation, and the placental index was recorded. In the micronucleus test, 2000 polychromatic erythrocytes (PCE) per animal, obtained from bone marrow, were scored. Results The results showed that exposure of the females during the pre- and post-implantation periods did not significantly alter the reproductive capacity (p<0.05); however, in higher dose (three times human dose)reduction of fetal weight was observed . There was no difference between the control and phytotherapeutic preparation (p>0.05) in terms of the average number of micronucleated polychromatic erythrocytes. ConclusionsAlthough folk medicine suggests that the Água Inglesa® preparation is useful as a female fertility stimulant, no such effect was confirmed in mice.

Anti-diabetic Activity of Aqueous Extracts of Vitex doniana Leaves and Cinchona calisaya Bark in Alloxan–Induced Diabetic Rats

Vitex doniana Sweet and Cinchona calisaya WEED are tropical medicinal plants endued with important pharmacological properties. The effects of aqueous extracts of V. doniana leaves and C. calisaya bark on alloxan-induced diabetes mellitus in Wistar albino rats were evaluated. Diabetes mellitus was induced by a single intraperitoneal ( i.p) injection of 150 mg/kg body wt of alloxan monohydrate. The aqueous extracts of V. doniana leaves and C. calisaya bark were administered intraperitoneally to four diabetic groups at same doses of 50 and 100 mg/kg body wt. The actions of the extracts were compared with that of the standard oral hypoglycaemic agent, glibenclamide. Both extracts caused significant (p < 0.001) decreases in blood sugar levels of the rats at both doses tested. At 50 mg/kg body wt. V. doniana leaf extract produced 82.9% reduction in blood sugar level (i.e from 492.8 to 84.5 mg/dl) after four days whereas, C. calisaya caused 64.4% decrease. Unlike C. calisaya bark, V. doniana at both doses tested, was more potent than the reference drug, glibenclamide (0.3 mg/ kg body wt.). The antidiabetic activity of V. doniana did not vary with the dose, whereas the observed effect of C. calisaya decreased with increase in dose. C. calisaya exhibited higher antidiabetic activity at a lower dose of 50 mg/kg body wt. Both medicinal plants therefore possess valuable antidiabetic property. Their effects on the antioxidant status were also investigated. V. doniana and C. calisaya extracts Research Article International Journal of TROPICAL DISEASE & Health, 2(4): 290-300, 2012 291 caused increases in the activity of SOD and lipid peroxidation when compared with control, but the increases were lower than that produced by alloxan, indicating attenuation of free radical generation. Quantitative phytochemical analyses of both extracts showed the presence of saponins(0.92%), flavonoids(7.05%), alkaloids(1.8%), and cardiac glycosides(2.8%) in V. doniana, whereas saponins(2.0%), flavonoids(5.0%), alkaloids(6.0%), and cardiac glycosides(3.54%) were detected in C. calisaya.

Nature’s Chiral Catalyst and Anti-Malarial Agent: Isolation and Structure Elucidation of Cinchonine and Quinine from Cinchona calisaya

Nature is a well-recognized source of compounds of interest, but access is often an issue. One pertinent example is the cinchona alkaloids from the bark of Cinchona calisaya. In this experiment, students at the third-year undergraduate level undertake the selective isolation and characterization of two of the four main alkaloids present in the bark. Beginning with powdered bark, acid–base extraction, followed by selective crystallization, serves to yield cinchonine, nature’s chiral catalyst, from the complex mixture. Slow crystallization provides suitable quality crystals for X-ray analysis. Students readily appreciate the three-dimensional nature of this chiral catalyst, which aids subsequent NMR spectroscopic analysis. Manipulation of the mother liquor by thin-layer and flash column chromatographic techniques proves a simple but elegant method to furnish quinine, nature’s anti-malarial agent. Both alkaloids are treated to an intensive structure elucidation workshop comprising 1- and 2-dimensional NMR, i...

Synthesis of triazol derivatives of lupeol with potential antimalarial activity

The goal of this project is synthesize and characterization of derivatives of lupeol and evaluated antimalarial activity. Historically, plants are important source of antimalarial medicines, highlighting quinine ( 1 ) (Figure 1), an important alkaloid from the Cinchona calisaya bark. This compound was an important model for cloroquine synthesis, a drug that was widely used in malaria treatment. In addition, one of the principal medicines used today is artemisinine, isolated from the Chinese plant Artemisia annua L ( 2 ) (Figure 1), and their semi synthetic derivatives (artesunate, artemeter, arteter). However, the malaria parasite has already shown resistance to most of these current drugs and the search for new candidates is essential. Lupeol ( 3 ) (Figura 1) is a compound that occurs in many plant species and discloses antimalarial, antiinflamatoryl and antitumoral activities. Considering its potential as a lead antimalarial molecule, we focused our work in the synthesis of new lupeol derivatives with increased antimalarial activity(scheme 1).

Tree invasion in managed tropical forests facilitates endemic species

AbstractAim To determine whether different abundances of introduced species of Cinchona (Rubiaceae) affect species composition and facilitate species richness in managed tropical forests, to test whether any facilitative effects on understorey species depend on forest type, and to investigate whether facilitative effects can be attributed to the ‘substitutive facilitation model’.Location Makawao Forest Reserve on Maui, Hawai’i, USA.Methods Cinchona species (Cinchona pubescens and Cinchona calisaya) were mapped within various forest types. In three forest types (ageing Eucalyptus and Pinus plantations, and near‐natural Acacia koa forests), we analysed environmental parameters (e.g. canopy cover, litter cover, pH value and soil depth) and the species composition of Cinchona‐invaded and non‐invaded plots; data were compared based on Cinchona cover and forest types. Habitat modelling for several endemic species and tree ferns was carried out to test whether Cinchona cover is an important variable for the probability of occurrence of these endemics.Results Cinchona species have naturalized mainly in Eucalyptus and Pinus plantations and Acacia koa forests and here add an additional shrub layer. In contrast to other studies, we revealed facilitative effects of Cinchona on native species within all forest types. Species richness is about 20% higher in invaded plots than in non‐invaded plots, and these show a nearly 50% higher proportion of endemic species, including tree ferns. The proportion of endemics even increases with increasing Cinchona cover. For several endemics, Cinchona is found to be an important variable for the probability of occurrence, and the removal of Cinchona cover as an explanatory variable lowers the model fit. In addition to Cinchona, variables delineating vegetation structure and light availability have a strong effect on the model fit.Main conclusions In the structurally simplified Hawaiian forests studied, Cinchona facilitated endemic species in accordance with the ‘substitutive facilitation model’. This contrasts with the results of an earlier study in the naturally treeless Galápagos highlands, which revealed a sharp decrease in the abundance of endemics under Cinchona canopy. These results illustrate that, through the same structural change (addition of a vegetation layer), an invasive species may exert divergent effects across different ecosystem types. The facilitation of endemic understorey species by invasive tree species in managed forests leads to a dilemma in conservation but also to new perspectives for ecosystem restoration.

On Cinchona Calisaya, var. Ledgeriana, How., and C. Ledgeriana (Moens).

Journal Article On Cinchona Calisaya, var. Ledgeriana, How., and C. Ledgeriana (Moens) Get access John Eliot Howard, F.R.S., F.L.S. John Eliot Howard, F.R.S., F.L.S. Search for other works by this author on: Oxford Academic Google Scholar Botanical Journal of the Linnean Society, Volume 20, Issue 129, September 1883, Pages 317–329, https://doi.org/10.1111/j.1095-8339.1883.tb00671.x Published: 05 January 2009