EXPLORING THE THERAPEUTIC POTENTIAL OF STRYCHNOS PSEUDOQUINA IN THE TREATMENT OF CHRONIC DISEASES

Objective: The objective of the study is to investigate the evidence of the therapeutic potential of * Strychnos pseudoquina * in the treatment of chronic diseases, with the aim of compiling and critically evaluating the data, identifying gaps in current knowledge, and suggesting directions for future research. Method: The methodology adopted for the research involved an integrative review of both qualitative and quantitative nature, covering the last 10 years, from 2014 to 2024. Articles were searched in the LILACS, PubMed, SciELO, and Cochrane databases, resulting in six selected articles. Results and Discussion: The results show that Strychnos pseudoquina possesses biological activities such as effects against leishmaniasis, antitumor, anti-inflammatory, antioxidant, and antiviral properties. Traditionally used in Brazil for various health problems, the plant has great potential in popular medicine. Additional studies are needed to determine safe dosages and explore its clinical potential in the treatment of chronic diseases.


INTRODUCTION
The Brazilian flora is an invaluable source of medicinal plants with therapeutic potentials that have not yet been fully explored.Among these plants, Strychnos pseudoquina, commonly known as quina-do-cerrado, stands out.This tree, native to the Brazilian cerrado, has been widely used in popular medicine as a bitter tonic and for treating fevers, as well as alleviating spleen, liver, and stomach problems (Grimaldi & Tesh, 1993).S. pseudoquina is rich in bioactive compounds, such as alkaloids and flavonoids, which exhibit a variety of promising biological activities (WHO, 2010).
Phytochemical studies conducted on S. pseudoquina have demonstrated the presence of various alkaloids and flavonoids, substances with significant therapeutic properties (Petersen, 2009).Pharmacological research has reported the plant's anti-ulcer, anti-leishmaniasis, hypoglycemic, and genotoxic effects (Grimaldi & Tesh, 1993;WHO, 2010;Petersen, 2009;Ready, 2010).However, the potential of S. pseudoquina in the treatment of chronic diseases, particularly its anti-inflammatory and analgesic activities, still requires further investigation (Ready, 2010).
The Brazilian alkaloids present in Strychnos pseudoquina offer a promising source of new compounds for the treatment of chronic diseases (WHO, 2010).The search for new, effective, and safe therapies is ongoing, especially for chronic conditions that affect a large part 4 of the population.Natural products, like those found in S. pseudoquina, provide a rich and diverse source of new bioactive compounds that can be developed into effective treatments for various diseases (Petersen, 2009).
Better understanding the medicinal properties of Strychnos pseudoquina can open new pathways for developing plant-based treatments, offering natural alternatives for managing chronic diseases (Grimaldi & Tesh, 1993).Investigating the anti-inflammatory and analgesic properties of this plant can significantly expand the available therapeutic options, providing benefits for both science and medical practice (WHO, 2010).
By exploring the potential of the Brazilian alkaloids present in Strychnos pseudoquina, this study aims to contribute to the discovery of new effective treatments for chronic diseases (Petersen, 2009).In this context, the objective of this article is to investigate the existing evidence on the therapeutic potential of Strychnos pseudoquina in the treatment of chronic diseases.

METHODOLOGY
The present study consists of an integrative review.The research method and filter used covered the last 10 years, from 2014 to 2024, with the descriptors "Strychnos pseudoquina", "Anti-inflammatory activity," and "Analgesic activity," and the Boolean operators "AND" and "OR."Using the descriptor "Strychnos pseudoquina" in the PubMed database, a total of 24 articles were found, with 6 articles in the last 10 years, available in full text for free, free text, or abstract, in English, Portuguese, or Spanish.This descriptor combined with the Boolean operator "AND" and the descriptors "Anti-inflammatory activity" OR "Analgesic activity," reduced this number to 1 article, which was selected, totaling 5 articles selected for the study, out of the 6 total articles from the PubMed database.In the Regional Portal of BVS (Virtual Health Library) in the LILACS (Latin American and Caribbean Literature in Health Sciences) database, using the descriptor "Strychnos pseudoquina," 6 articles were obtained.When applying the period filter for the last 10 years, 1 article was found.Using the descriptors "Strychnos pseudoquina" AND (Anti-inflammatory activity OR Analgesic activity), no articles were found, necessitating that the descriptor "Strychnos pseudoquina" be used alone, resulting in 1 article in the LILACS database, which was selected as it was related to the study objective.In the Cochrane database, using the descriptor "Strychnos pseudoquina" OR "Quina-do-cerrado," no articles were found in the last do-cerrado," 6 articles were found, but when applying the inclusion criterion of the last 10 years, no articles were found.
Inclusion criteria considered original articles that addressed the researched topic and provided full access to the study content, published from 2014 to 2024, in English, Spanish, or Portuguese, and related to the study objective.Exclusion criteria were imposed on works not in English, Spanish, or Portuguese, and not related to the proposed theme.The searches were conducted independently, and the articles had to contain at least one keyword included in the title and/or abstract, exclusively related to "Strychnos pseudoquina".
Through the conducted search, a total of 36 articles were found, with 24 articles from the PubMed database, 6 articles from the LILACS database, 6 articles from the SciELO database, and no articles from the Cochrane database.After reading the title and/or abstract, excluding duplicate studies and those that did not meet the inclusion criteria and study objective, a total of 6 articles were selected for the integrative review, with 5 articles from the PubMed database and 1 article from the LILACS database, as shown in the flowchart of the selected articles presented in Figure 1.

Flowchart of Article Selection Included in the Review
Fonte: Authors, 2024.

RESULTS AND DISCUSSIONS
The description of the articles included in this integrative review considers criteria such as the title of the work, the authors, the year of publication, as well as the primary and secondary outcomes in relation to Strychnos pseudoquina, as detailed in Table 1.The selected studies presented appropriate methodologies for the research, demonstrating the characteristics and therapeutic properties of quina-do-cerrado in different pathologies.

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The Cerrado, the second-largest biome in Brazil, is notable for its rich biodiversity and high degree of endemism, making it a crucial area for conservation.Among the native plants of the Cerrado, Strychnos pseudoquina, commonly known as "quina-do-cerrado," stands out for its alkaloids and flavonoids (Boff et al., 2016;Silva et al., 2023).
The phytochemical analysis of S. pseudoquina, conducted in the study by Silva et al. (2023), reveals a variety of secondary metabolites, such as flavonoids, including quercetin and luteolin, which belong to the group of flavones.Silva et al. (2023) emphasize 3-Omethylquercetin, a flavonoid with a methoxy group at the 3 position of the C ring, found in S.
pseudoquina.This compound has demonstrated multiple biological activities, including antileishmanial and antitumor properties, showing significant efficacy against breast and lung cancer cells.The presence of functional groups, such as methoxy, enhances the lipophilicity and bioavailability of the compounds, increasing their therapeutic efficacy (Silva et al., 2023).Sarandy et al. (2017) identified the presence of tannins, flavonoids, and alkaloids in the plant extract, highlighting chlorogenic acid, known for its antioxidant and wound-healing properties.The topical application of the extract on wounds resulted in a reduction of wound area, increased vascularization, and improved collagen synthesis in diabetic wound models.
These effects are attributed to the extract's ability to neutralize free radicals and increase the activity of antioxidant enzymes such as SOD and CAT, reducing levels of MDA and carbonylated proteins (Sarandy et al., 2017).
In the context of visceral leishmaniasis, a chronic disease, Lage et al. (2015) evaluated the antileishmanial activity of the flavonoid strychnobiflavone against Leishmania infantum.
The results showed that this flavonoid causes a significant reduction in infected macrophages and depolarization of the mitochondrial membrane in Leishmania, suggesting the mitochondria as the target organelle.Additionally, strychnobiflavone exhibited low toxicity to murine macrophages and minimal hemolytic activity, indicating additional safety in terms of toxicity to blood cells (Lage et al., 2015).
The study by Boff et al. (2023), on the mechanism of action of Strychnos pseudoquina against the herpes virus, revealed that the standardized ethyl acetate extract (SEAE) and strychnobiflavone (SBF) interfere at various stages of the HSV replication cycle, mainly adsorption, post-adsorption, and penetration, as well as inhibiting the expression of β and γ viral proteins.Direct inactivation of viral particles was also observed.Additionally, both flavonoids selectively inhibited MCP-1, a feature that may be beneficial in the development of new anti-HSV agents, as herpes labialis and genital lesions are accompanied by an inflammatory process (Boff et al., 2016).Grosso, to treat digestive problems, act as a vermifuge, depurative, and appetite stimulant, among other uses.The plant's efficacy in combating anemia and its anti-inflammatory, antiherpes, and gastroprotective properties were also reported (Costa et al., 2017;Miguéis et al., 2019).
Despite its therapeutic potential, it is important to consider the risks associated with the use of Strychnos pseudoquina, especially due to the presence of alkaloids that can have toxic effects.The toxicity of Strychnos species varies according to the part of the plant used, and the presence of strychnine in some species can cause severe symptoms such as seizures and death at high doses (Sarandy et al., 2017).Santos et al. (2016) reported that the leaf extract of S. pseudoquina demonstrated cytotoxicity in Salmonella TA98 strains at doses of 26.6 mg/plate, highlighting the need for careful evaluation of the safety and toxicity of the compounds before clinical use.
Drug interaction is another relevant aspect.The flavonoids present in S. pseudoquina, such as 3-O-methylquercetin, can interact with conventional medications, potentiating or inhibiting their effects.For example, luteolin, when administered with conventional chemotherapy, can increase anticancer effects but may also interfere with other pharmacological treatments, requiring careful monitoring (Sarandy et al., 2017;Silva et al., 2023).
In conclusion, studies on the use of S. pseudoquina are promising (Sarandy et al., 2017;Silva et al., 2023), highlighting the therapeutic potential of Strychnos pseudoquina in treating chronic diseases due to the presence of secondary metabolites with promising pharmacological properties.However, the safety and toxicity of these compounds, as well as their drug interactions, need to be rigorously evaluated.Elucidation of molecular mechanisms and additional studies on the pharmacokinetics and safety profile of these compounds will provide valuable insights for the broader clinical applicability of S. pseudoquina in treating chronic diseases.

CONCLUSION
Strychnos pseudoquina emerges as a plant of significant pharmacological interest, notable for its vast spectrum of secondary metabolites, such as flavonoids and alkaloids, which Exploring the Therapeutic Potential of Strychnos Pseudoquina In the Treatment of Chronic Diseases ___________________________________________________________________________ Rev. Gest.Soc.Ambient.| Miami | v.18.n.9 | p.1-12 | e08314 | 2024.

Figure 2
Figure 2Distribution of Strychnos pseudoquina in the Cerrado Exploring the Therapeutic Potential of Strychnos Pseudoquina In the Treatment of Chronic Diseases ___________________________________________________________________________ Rev. Gest.Soc.Ambient.| Miami | v.18.n.9 | p.1-12 | e08314 | 2024.10 Additionally, Strychnos pseudoquina is used in traditional medicine for treating various conditions.Miguéis et al. (2019) documented its use in the rural community of Bananal, Mato exhibit remarkable therapeutic properties.Recent studies indicate that compounds like 3-O-Exploring the Therapeutic Potential of Strychnos Pseudoquina In the Treatment of Chronic Diseases ___________________________________________________________________________ Rev. Gest.Soc.Ambient.| Miami | v.18.n.9 | p.1-12 | e08314 | 2024.11 methylquercetin and strychnobiflavone possess diverse biological activities, including antileishmanial, antitumor, anti-inflammatory, antioxidant, and antiviral effects.Furthermore, the plant has been traditionally used in various Brazilian communities to treat a variety of health conditions, corroborating its potential in the context of folk medicine.However, despite its promising therapeutic potential, it is essential to consider the risks associated with the use of S. pseudoquina, especially due to the presence of alkaloids that may exhibit toxicity.The safety of compounds derived from this plant must be rigorously investigated, taking into account the variations in toxicity between different parts of the plant and the potential for drug interactions with conventional treatments.Studies highlight the need for cautious approaches to ensure that therapeutic benefits are achieved without compromising patient safety.Therefore, future studies should focus on elucidating the molecular mechanisms of action of the compounds from S. pseudoquina, as well as thoroughly evaluating their pharmacokinetics and safety profiles.Additional research is needed to determine safe and effective doses and to fully explore the clinical potential of the plant in treating chronic diseases.Through these investigations, Strychnos pseudoquina can be more broadly and safely integrated into clinical practice, offering a new perspective for the development of therapies based on natural products.

Table 1
Analysis of Selected ArticlesThe species Strychnos pseudoquina (quina) was indicated for the treatment of various bodily issues, including digestive problems, as a vermifuge, depurative, appetite stimulant, for anemia, diabetes, cough, and headaches.However, the most frequent citation was for digestive system issues.This use aligns with studies that confirm the gastroprotective activity of Strychnos pseudoquina.
Exploring the Therapeutic Potential of Strychnos Pseudoquina In the Treatment of Chronic Diseases ___________________________________________________________________________ Rev. Gest.Soc.Ambient.| Miami | v.18.n.9 | p.1-12 | e08314 | 2024.Plants from the Cerrado can be used as a source of potential anticancer compounds.3-O-methylquercetin was extracted and isolated from S. pseudoquina A.St.-Hil.(Loganiaceae) using a chromatography technique, yielding approximately 0.07 mg/g.The cytotoxicity evaluation of 3-Omethylquercetin, derived from S. pseudoquina A.St.-Hil., was juxtaposed with findings in the literature on quercetin and luteolin, confirming its previously reported antitumor efficacy.Fonte: Authors, 2024.