Evaluation Of The Reproductive And Developmental Toxicities Of The Aqueous Extract Of Labisia Pumila Var. Alata In Female Rats

Labisia pumi/a var. a/ata (LPA) atau Kacip Fatimah disenaraikan sebagai salah satu spesis utama oleh kerajaan Malaysia untuk dijalankan kajian saintifik pelbagai disiplin ke arah pembangunan ubatan herba tempatan berasaskan bukti saintifik. Kajian yang dihuraikan di dalam tesis ini adalah sebahagian daripada kajian pra klinikal ke atas LPA untuk menilai profil keselamatannya. Tujuan kajian ini adalah untuk menentukan potensi kesan sediaan komersial ekstrak air LPA ke atas ketoksikan reproduktif dan pertumbuhan pada tikus betina Sprague Dawley. Kajian permulaan dijalankan dengan menggunakan ekstrak air tidak terpiawai LPA pada dos 2, 20, 200 dan 400 mg/kg/hari. Sediaan komersial ekstrak air terpiawai LPA, didaftarkan sebagai Biolabisia® pad a dos 2, 20, 200, 400, 1000 mg/kg/hari atau air suling (kawalan) diberikan kepada tikus secara gavaging dalam kajian utama. Kajian Teratogenik dijalankan dengan memberikan rawatan Biolabisia® kepada tikus hamil semasa peringkat organogenesis. Rawatan ke atas tikus diberi sejak sebelum tempoh mengawan sehingga hari ke-7 waktu laktasi dalam kajian Ketoksikan reproduktif dan sebelum mengawan sehingga hari ke-15 kehamilan bagi kajian Kesuburan. Labisia pumi/a var, a/ala (LPA) or Kacip Fatimah has been listed by the government of Malaysia as one of the priority species for a multi-disciplinary scientific study towards the development of scientific, evidence-based herbal medicine. The present study described in this thesis is part of the preclinical assessment of LPA to evaluate its safety profile. The aims of this study were to evaluate the potential effects of aqueous extract of LPA on reproductive and developmental toxicities in Sprague Dawley rats. A preliminary study was conducted using unstandardised extract of LPA at 2, 20, 200 and 400 mg/kg/day. Commercially prepared standard aqueous extract of LPA, registered as Biolabisia® at the doses of 2,20, 200,400, 1000 mg/kg/day or distilled water (control) were administered by gavaging to animals during the main studies. The Teratogenic study was conducted by treating pregnant animals with Biolabisia® during the period of organogenesis. Treatments of animals began from the time prior to mating until lactational periods of seven days in the Reproductive toxicity study and from before mating up to day 15 of pregnancy in the Fertility study

The effects of Malaysian herb, Labisia pumila var. alata on oestrous cyclicity and reproductive parameters of nulliparous rats

Numerous nutraceutical products containing the powdered or extracted parts of Labisia pumila (Myrsinaceae) have been widely available for years in Malaysia, aimed at women of reproductive age. However, there is scarce of information concerning the effects of this plant on the reproductive function of nulliparous females prior to the present study. The toxicity potential of Labisia pumila var. alata (LPA) on oestrous cycle and reproductive parameters was evaluated in groups of 40 virgin rats. They were administered with LPA at the doses of 0 (control), 20, 200 or 1000 mg/kg/day for duration of three weeks. The results obtained indicated that the administration of LPA at all dose levels did not cause mortality nor show noticeably any treatment-related signs of toxicity on the physical appearance, behaviour and body weight of all the rats studied. The pattern and length of oestrous cyclicity as well as the changes in reproductive hormones were statistically comparable among groups. No indications of abnormalities in the histology of uterus and vagina were observed. However, the presence of ovarian follicular cysts has raised apprehension that requires further investigation. The current findings suggested that oral treatment of LPA were associated with toxicity concerns

Evaluation of the male and female fertility and teratogenic effects of Lignosus rhinocerotis (Cooke) Ryvarden in rats

Lignosus rhinocerotis (Cooke) Ryvarden (LR) or tiger milk mushroom has traditionally been used in Malaysia due to its abundant medicinal properties. The potential effects of LR on the male and female fertility and teratogenicity were investigated on rats. Male Sprague Dawley (10 rats/group) were orally administered with 0, 250, 500 and 1000 mg/kg/day of LR extract for 30 consecutive days. Female (5 rats/group) received the same treatment beginning the dioestrus of pre-mating, through mating periods and continuously up to day 20 of pregnancy while the rest of the females (5 rats/group) were left untreated. Evaluation on general health, behaviour, body weight and organ weights; reproductive and internal organs were carried out. Male fertility parameters such as the reproductive performance and hormones as well as sperm analysis were examined. Maternal gross assessment at autopsy and detailed foetal examination were conducted to determine the teratogenicity. The findings obtained on the male animals showed that no significant deleterious effects on the general health, body weight, reproductive and visceral organs weight, reproductive performance, hormones and sperm analysis of up to 1000 mg/kg/day daily doses of LR. Foetal parameters and gross examination of pregnant dams at autopsy showed that the extract did not affect the fertility of the rats and teratogenicity of the litters. Our findings showed that no treatment-related toxicity on the fertility of male and female rats in all groups following LR treatment. The herbal extract also did not result in teratogenic effects on the offspring of the treated dams

Circulating neonatal Nav1.5 (nNav1.5) antigen and anti-nNav1.5 antibodies as potential biomarkers for breast cancer metastasis

Neonatal Nav1.5 (nNav1.5) has been known to potentiate breast cancer (BCa) metastasis. The detection of anti-nNav1.5 antibodies (anti-nNav1.5-Ab) reflects the immunogenicity of nNav1.5. However, the presences of circulating nNav1.5 antigen and anti-nNav1.5-Ab in the context of BCa metastasis have not been explored yet. Therefore, the study has attempted to conduct such an investigation using both blood samples from 4T1 orthotopic mice and BCa patients. In the preclinical study, forty female BALB/c mice were divided into three groups: 4T1 orthotopic BCa mice (n=17), control mice (n=20) and positive control mice (n=3). After tumour development, the mice were sacrificed to obtain target organs, whole blood, and serum. Histopathology, cytokine analyses, real-time PCR, and indirect ELISA were performed. Histopathology and cytokine analyses showed the establishment of metastasis in 4T1 orthotopic mice. The concentration of vascular endothelial growth factor (VEGF) was significantly higher in the 4T1 orthotopic mice (P<0.0001****). Circulating nNav1.5 antigen and anti-nNav1.5-Ab were detected in 4T1 orthotopic mice, using real-time PCR and indirect ELISA, respectively. Furthermore, there was an inverse relationship between anti-nNav1.5-Ab and the total metastatic foci (P=0.0485*, r=-0.7306). In the clinical study, 32 BCa patients were grouped based on their stages: early-invasive (n=15) and advanced (n=17) stages. Approximately 3 mL of blood was withdrawn, and only indirect ELISA was conducted. The clinical study showed that BCa patients of advanced-stages portrayed higher expression of anti-nNav1.5-Ab compared to early stages of BCa (P =0.0110*). In conclusion, the detection of nNav1.5 antigen and anti-nNav1.5-Ab was consistent with the presence of BCa metastasis

EVALUATION OF THE TERATOGENICITY OF AQUEOUS EXTRACT OF Labisia pumila var. alata IN RAT

A dose range study to assess the teratogenic potential of aqueous extract of Labisia pumila var. alata (Kacip Fatimah) was conducted in rodents. The extract at doses of 0 (control), 2, 20, 200, 400, 1000 mg/kg/day were respectively administered by gavaging to 6 groups of pregnant Sprague Dawley rats from day 6 through day 16 of pregnancy and sacrificed on day 21. No significant agent-related effects including changes in maternal body weight (MBW) nor weight gain were observed. The corrected maternal body weights (CMBW) were slightly higher in animals receiving low dose extracts (2 mg/kg/day) as compared to all groups of animals. However, body weight differences were not statistically significant. Gravid uterine weight, number of corpora lutea, number of implantation sites, percentage of foetal resorptions, number of life foetuses, foetal weight and foetal sex ratio showed no significant differences among all group animals. None of the foetuses from all dams showed evidence of external congenital malformations. These findings may suggest that aqueous extracts of Labisia pumila var. alata up to 1000 mg/kg/day statistically do not show any significant teratogenic effects in rats but do affect the maternal body weight and this is dose dependent

Evaluation of the teratogenicity of aqueous extract of labisia pumila var. alata in rats

A dose range study. to assess the teratogenic potential of aqueous extract of Labisia pumila var. alata (Kacip Fatimah) was conducted in rodents. The extract at doses of 0 (control), 2, 20, 200, 400, 1000 mglkglday were respectively administered by gavaging to 6 groups of pregnant Sprague Dawley rats from day 6 through day 16 of pregnancy and sacrificed on day 21. No significant agent-related effects including changes in maternal body weight (MBW) nor weight gain were observed. The corrected maternal body weights (CMBW) were slightly higher in animals receiving low dose extracts (2 mglkglday) as compared to all groups of animals. However, body weight differences were not statistically significant .. Gravid uterine weight, number of corpora lutea, number of implantation sites, percentage of foetal resorptlons, number of life foetuses, foetal weight and foetal sex ratio showed i10 significant differences among all group animals. None of the foetuses from all dams showed evidence of external congenital malformations. These findings may suggest that aqueous extracts ofLabisia pumila var. alata up to 1000 mglkglday ~tatlstically do not show any significant teratogenic effects In rats but do affect the maternal body weight and this is dose dependen

Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives

Nav1.5 is one of the nine voltage-gated sodium channel-alpha subunit (VGSC-&alpha;) family members. The Nav1.5 channel typically carries an inward sodium ion current that depolarises the membrane potential during the upstroke of the cardiac action potential. The neonatal isoform of Nav1.5, nNav1.5, is produced via VGSC-&alpha; alternative splicing. nNav1.5 is known to potentiate breast cancer metastasis. Despite their well-known biological functions, the immunological perspectives of these channels are poorly explored. The current review has attempted to summarise the triad between Nav1.5 (nNav1.5), breast cancer, and the immune system. To date, there is no such review available that encompasses these three components as most reviews focus on the molecular and pharmacological prospects of Nav1.5. This review is divided into three major subsections: (1) the review highlights the roles of Nav1.5 and nNav1.5 in potentiating the progression of breast cancer, (2) focuses on the general connection between breast cancer and the immune system, and finally (3) the review emphasises the involvements of Nav1.5 and nNav1.5 in the functionality of the immune system and the immunogenicity. Compared to the other subsections, section three is pretty unexploited; it would be interesting to study this subsection as it completes the triad

General toxicity studies of alpha mangostin from Garcinia mangostana: A systematic review

Alpha mangostin (AM), the main xanthone derivative contained in mangosteen pericarp (Garcinia mangostana/GM), has many pharmacological activities such as antioxidant, antiproliferation, antiinflammatory, and anticancer. Several general toxicity studies of AM have been previously reported to assess the safety profile of AM. Toxicity studies were carried out by various methods such as on test animals, interventions, and various routes of administration, but the test results have not been well documented. Our study aimed to systematically summarizes research on the safety profile of GM containing AM through general toxicity tests to get the LD50 and NOAEL values, and so, can be used as a database related to AM toxicity profiles. This could facilitate other researchers in determining further development of GM-or-AM-based products. Pubmed, Google scholar, ScienceDirect, and EBSCO were chosen to collect the articles while ARRIVE 2.0 was used to evaluate the quality and risk-of-bias of the in vivo toxicity studies included in this systematic review. A total of 20 articles met the eligibility criteria and were reviewed to predict the LD50 and NOAEL of AM. The results showed that the LD50 of AM is between >15.480 mg/kgBW to ≤6000 mg/kgBW while the NOAEL value is between <100 and ≤2000 mg/kgBW

Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyperresponsiveness in a murine model of asthma.

Lignosus rhinocerotis Cooke. (L. rhinocerotis) is a medicinal mushroom traditionally used in the treatment of asthma and several other diseases by the indigenous communities in Malaysia. In this study, the effects of L. rhinocerotis on allergic airway inflammation and hyperresponsiveness were investigated. L. rhinocerotis extract (LRE) was prepared by hot water extraction using soxhlet. Airway hyperresponsiveness (AHR) study was performed in house dust mite (HDM)-induced asthma in Balb/c mice while airway inflammation study was performed in ovalbumin (OVA)-induced asthma in Sprague-Dawley rats. Treatment with different doses of LRE (125, 250 and 500 mg/kg) significantly inhibited AHR in HDM-induced mice. Treatment with LRE also significantly decreased the elevated IgE in serum, Th2 cytokines in bronchoalveolar lavage fluid and ameliorated OVA-induced histological changes in rats by attenuating leukocyte infiltration, mucus hypersecretion and goblet cell hyperplasia in the lungs. LRE also significantly reduced the number of eosinophils and neutrophils in BALF. Interestingly, a significant reduction of the FOXP3+ regulatory T lymphocytes was observed following OVA induction, but the cells were significantly elevated with LRE treatment. Subsequent analyses on gene expression revealed regulation of several important genes i.e. IL17A, ADAM33, CCL5, IL4, CCR3, CCR8, PMCH, CCL22, IFNG, CCL17, CCR4, PRG2, FCER1A, CLCA1, CHIA and Cma1 which were up-regulated following OVA induction but down-regulated following treatment with LRE. In conclusion, LRE alleviates allergy airway inflammation and hyperresponsiveness, thus suggesting its therapeutic potential as a new armamentarium against allergic asthma