Potential Combination of Xanthone Compounds from Mangosteen Fruit (Garcinia mangostana) With Eugenol Compounds in Basic Leaf (Ocimum sanctum) As Alternative Therapy in Preeclampsia

Preeclampsia is a hyperdynamic condition that is syndromed by hypertension and proteinuria after 20 weeks of pregnancy. Preeclampsia incident is the first cause of 68 % number morbidity/mortality maternity and fetus in the world. Preeclampsia is related to the disability of physiology adaptation that can decrease perfusion of uteroplacental. Xanthone derivatives in mangosteen have been reported to possess a wide range of biological properties, including antioxidant and antihypertensive activities. Eugenol is a primary component of basil oil. It is known for its antioxidant, antiinflammatory, and vasorelaxant actions. These beneficial effects of eugenol make it an excellent therapeutic candidate for the treatment of hypertensive disorders of pregnancy. This study wants to analyze the best available research evidence on the potential combination of xanthone compounds from mangosteen fruit (Garcinia mangostana) with eugenol compounds in basil leaf (Ocimum sanctum) as an alternative therapy in preeclampsia. A literature review was conducted in the electronic databases PubMed and Google Scholar using the index terms "xanthone" and "eugenol" and "hypertension" and "preeclampsia." All types of studies were included for this study, such as randomized controlled trials, systematic reviews, literature reviews, and pilot studies published between 2010 and 2021. Articles which not written in English were excluded from the study. This search resulted in 10 papers. Antioxidant properties of mangosteen peel extract compounds derived from xanthone, the most significant component is α-mangosteen and γ-mangosteen. Eugenol is vasorelaxant action by increasing the expression of its target genes, Sarco/endoplasmic reticulum Ca2+-ATPase and adequate potassium-calciumactivated potassium channels channel, thereby relaxing vascular smooth muscle cells and decreasing blood pressure. With this review, we suggest that eugenol, which is a vasorelaxant combined with xanthone which is an antioxidant by obstructing free radical and oxidative stress, can be a potent therapeutic for preeclampsia and intend to motivate researchers (e.g., chemistry, biology, pharmaceutical, and therapeutic areas) to provide evidence of these compounds for the management of preeclampsia.


Introduction
Preeclampsia is a pregnancy syndrome that affects multiple organ systems, characterized by hypertension and proteinuria after 20 weeks.
Globally, the incidence of preeclampsia ranges from 5-7% in pregnancy. In developing countries like Indonesia, the number is relatively high, namely about 5-10% of pregnancies, and contributes to high maternal and fetal morbidity and mortality. 8 Placental trophoblast cells invade the uterine arteries (spiral arteries in humans) during embryo implantation and induce its remodeling while obliterating the tunica media of the myometrial spiral arteries, which allows the arteries to accommodate increased blood flow to nourish the developing fetus. This abnormal spiral artery remodeling was seen and described over five decades ago in pregnant women who were hypertensive which, if not treated, may lead to preeclampsia and eclampsia, a severe form of hypertension and convulsions, and may also

Eureka Herba Indonesia
Journal Homepage: https://eurekabiomedical.com/index.php/EHI consequent into coma and death. 8 Hemodynamic changes can occur in pregnant women with preeclampsia; decreasing placental perfusion will induce transcription factor HIF-1α.

Methods
The researcher searched for all studies Moreover, because these confounding factors are difficult to account for this study, the adjusted results were used and discussed in this article when available. In the first step, the researcher assesses the titles and abstracts of the studies to exclude reports based on the criteria. In the second step, the researcher read and evaluated the full-text studies that met the requirements.

Results
The randomized controlled clinical trial conducted in different countries such as Indonesia [8,11], Brazil [2,5], India [1,4,9], USA [3,6,10], Poland [7]. RCTs resulted that mangosteen, especially xanthone, has a potential antihypertensive activity. 5,6,7,9,11 One experimental study resulted that mangosteen has a potential antihypertensive activity in pregnant women. 8 Two experimental studies and One RCTs resulted from eugenol has a possible antihypertensive activity. 1 The trial duration was 30 days. ORAC is an antioxidant biomarker that was measured in both groups. It was found that after the 30-day trial, the group given the mangosteen has 15% more antioxidant capacity in the bloodstream than a group of placebo. The C-reactive protein level decreased 46% in the mangosteen group between the preintervention and postintervention. There were no side effects on hepatic and kidney functions.  A, B, C, and D). Group A has received 2520 mg/day GMLE with ACE-i/ ARB, Group B has received 2520 mg/day GMLE with CCB, Group C has received ACE-i with placebo, and Group D has received CCB with placebo Group A, which received GMLE with ACE-i/ARB, is the best group to reduce systolic blood pressure. In Group A, diastolic blood pressure was also lower, although this change did not differ from another group.The reducing effect in group A was better than other group, p = 0.028, Interestingly, In Group A, we found that there was a significance decreasing in HsCRP compared with B, C,and D (−101 ± 10,3 pg/ml, -96 ± 6,4 pg/ml, -28 ± 12,2 pg/ml, -25 ± 3,7 pg/ml, respectively, p = 0,01). The reducing effect of TNF-a,plasma IL-6 and IL-1 concentration was significantly lower in group A compared with other group (p = 0,01, p = 0,002, p = 0,005, respectively). It should be noted that the use of a drug must see the value of its toxicity. Xie

Conclusion
This study showed that eugenol is a potent and