Psidium guajava L. : History
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Psidium guajava L. (guava) is a small tree known for its fruit flavor that is cultivated almost around the globe in tropical areas. Its fruit is amazingly rich in antioxidants, vitamin C, potassium, and dietary fiber. Psidium guajava L., commonly known as guava is a small tree, and is grown in tropical areas of world due to its fruits. Guava leaf tea and some complementary items are available in many stores in Japan, as it is considered that phenolic compounds of guava leaves can resolve particular health issues such as the modulation of blood sugar levels. In addition to being a healthy and tasty food, the fruit is an excellent source of dietary fiber. Eating guavas may aid healthy bowel movements and prevent constipation.

  • Psidium guajava L.
  • pharmacological activities
  • industrial application

1. Pharmacological Activities

1.1. Antidiabetic Potential of Leaf Extract

Literature search revealed that several studies have been carried out to evaluate pharmacological potential of guava leaves. The guava leaves have an ability to increase glycogen synthesis and halt the process of hepatic gluconeogenesis by regulating AMPK/ACC pathway in streptozotocin-induced diabetic rats, when orally administered as 200 mg/kg by weight [57]. It is further reported that guava leaves reduced triglycerides, phospholipids, free fatty acids, total cholesterol and LDL levels while HDL level was raised in STZ induced rats [57]. To validate the role of guava leaves in treatment of Diabetes Mellitus (DM), a novel purified heteropolysaccharide GP70-3M from the leaves was tested in vitro against α-glucosidase, which showed outstanding inhibitory activity with an IC50 value of 2.539 µM. This potential has been reported to be 1867 times greater than control acarbose (IC50 value of 4.744 mM). Different parts of the plant were screened for their diabetic inhibition (Table 7) [58].
Table 7. Anti-diabetic potential of different parts of P. guajava.

1.2. Anticonvulsant Effects

The P. guajava leaf ethanolic extract has been found to afford anti-convulsant activity; since it exerted dose dependent (200 mg/kg and 400 mg/kg) effect on seizures induced mice using MES as suggested by some parameters for example reduced hind-limb tonic extension (HLTE), increased percentage protection from induced MES convulsions. Anti-convulsant effect on Maximal Electrocshock (MES) mice model suggests that the extract has produced dose dependent anticonvulsant effect in albino mice. While in pentylenetetrazole (PTZ) induced mice model P. guajava extract prolonged the clonic convulsion latency, reduced convulsion duration in a dose dependent manner along with reduction in seizure score [60].

1.3. Antiproliferative Potential of Essential Oils from P. guajava Leaves Extracts

Essential oil obtained from leaves of P. guajava was evaluated for its antiproliferative activity against human gliobastoma (M059J), human cervical adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7) and normal human GM07492A cell lines, whereas lung fibroblasts cell line was used as control. The reported results showed that the oil exhibited significant IC50 values for M059J and MCF-7 compared to normal line as presented in Table 8 [61].
Table 8. IC50 and selectivity index (SI) of essential oil of P. guajava leaves (PG-EO) against diferent cell lines.

1.4. Antimutagenic Effect

The methanolic extract of P. guajava leaves tested against methyl sulfonate (MMS), sodium azide (NaN3), benzo(a)pyrene (BP) and 2-aminofluorene for its antimutagenic effect. The methanol extract of P. guajava leaf extract was found to inhibit 70% of mutagenesis at concentration of 80 mg/mL. This setup is on the basis that the phenolic contents present in P. guajava have broad-spectrum antimutagenic activity and could serve as potentially good Candidates for phytomedicine [25].

1.5. Antifungal Properties

Various published work revealed that P. guajava L. has also shown to possess some antifungal activities. Its tannins and flavonoid fraction were analyzed for antifungal activity using 21 different compounds in fraction of two, having phenolic compound in higher concentration. In an in vitro assay performed against three fungal strains of Candida i.e albicans, krusei and tropicalis through microdilution showed that IC50 values for these strains ranged from 69.29 to 3444.62 μg/mL for the isolated and combined fractions of flavonoids and tannins. While the reference compound fluconazole and combined fraction ranged from 1.57 to 925.56 μg/mL, which shows that natural products have some synergism with antifungal potential. The fractions were found to affect pleomorphism capacity as well along with inhibition of fungal strain in isolated form, enhancing the action potential of Fluconazole, reducing the concentration and hindering the morphological transition, one of the main virulence factor of Candida genus [62]. The P. guajava leaves extract was used for microbiological assays to determine IC50, inhibitory effect of associated fraction with Fluconazole against Candida species and cell viability curve through microdilution method. Antifungal bioassay performed on solid media by modifying morphological and fungicidal concentration and results ranged between 5.10 and 926.56 mg/mL revealed the effect of change in concentration effects the inhibition [21]. This suggests that P. brownianum and P. guajava can potentially be used to develop drugs to treat fungal infections [63,64].

1.6. Antiparasitic Potential

P. guajava L. and Psidium browninaum Mart ex DC leaf aqueous and hydroethanolic extracts were tested for their antiparasitic and cytotoxic potential against Leishmania braziliensis, Trypanosoma cruzi epimastigote forms, L. infantum promastigotes and fibroblasts at three different concentrations (250, 500 and 1000 μg/mL). The T. cruzi forms were not inhibited by the extracts from P. guajava L. P. guajava showed small amount of activity against both L. braziliensis and L. infantum. As for cytotoxicity aqueous decoction extract of P. browninaum showed highest percentage among all other extracts and showed mortality rate of 90.85% for fibroblast at 1000 μg/mL [65].

1.7. Anthelmintic Activity

The aqueous extract of P. guajava paralyzes the nematodes both Levamisole-sensitive and Levamisole-resistant strains of Caenorhabditis elegans, in a dose dependent manner. Different studies were carried out by applying concentration-dependent doses. At a concentration of 25 mg/mL of the P. guajava extract, 100% paralysis of the wild type worms was achieved with in 4 h. A similar effect was observed for N2 wild type and CB193 resistant worms and egg-laying ability was decreased by 40% at the same concentration. These reports disclose that P. guajava extracts have also potential anthelminic effect against nematodes [66]. Further these studies revealed the presence of triterpene responsible for anthelmintic activity. Therefore, it is also concluded that secondary metabolites from P. guajava leaves extract could serve as basis for antileishmanial drugs [67].

1.8. Antioxidant Potential

Phytochemistry of Guava showed the presence of flavonoids and phenolics, which is in agreement with antioxidant activity. The antioxidant activity for crude extract of peels, flesh and seed was 264.30 ± 5.39 μmol TE/g dw, 98.78 ± 3,40 μmol TE/g dw and 62.84 ± 2.81 μmol TE/g dw, respectively, which is nearly equal to the genotype known as Fan Retief and Advanced Selection. The crude extract of the peel part having highest antioxidant activity has a greater proportion of antioxidant compounds [68]. The products in P. guajava leaf tea (GLT) contain both phenolic forms i.e., soluble and insoluble-bound. The fermentation process via Saccharomyces cerevisiae and Monascus anka followed by hydrolysis through complex enzymes increases the soluble phenolic form. Free radical scavenging (DPPH) results of guava were found in close agreement with standard Trlox and ascorbic acid. The excellent IC50 in μM revealed the guava extract as potential anti-oxidant. Comparative studies on extracts and Trolox revealed the direct relationship with concentration. As the concentration was increased, the reducing ability was also enhanced and, like radical scavenging activity, SPFE reducing power was greater than rest of the extracts. The reducing power for SPFE = 97.86 mmol TE/g DM, SPF = 50.3 mmol TE/g DM, SPUF = 7.4 mmol TE/g DM. The reducing ability of soluble phenolics (SPF/SPFE) was higher than insoluble bound phenolics (IBF/IBFE) at same concentration. However, the reducing power for insoluble-bound phenolics of unfermented GLT (IBUF) was found to be 11.4 mmol TE/g DM which greater than IBF (2.9 mmol TE/g DM) and IBFE (3.5 mmol TE/g DM). When the extracts were tested for their inhibitory activity against α-glucosidase, the inhibitory effect was promisingly high for SPUF, but it was observed that it was much higher for fermented extract. The IC50 values for inhibition of α-glucosidase were in order SPFE (IC 50 = 11.8 µg/mL) > SPF (IC 50 = 19.2 µg/mL) > SPUF (IC 50 = 29.1 µg/mL). Moreover, insoluble-bound phenolics of fermented GLT (IBPF) and IBPFE have low inhibitory effect on α-glucosidase (i.e., IC50 = 104.4 µg/mL and IC 50 = 112.2 µg/mL respectively) as compared to insoluble-bound phenolics of unfermented GLT (IBPUF) having IC50 = 71.6 µg/mL. The IC50 value for positive control (acarbose) was significantly greater than all the extracts i.e., IC50 = 178.52 µg/mL [69].

1.9. Suppression of Osteoarthritis

The leaves extract from P. guajava and ellagic acid, a polyphenolic compound from the extract, have role in degeneration of aggrecan at the onset of osteoarthritis (OA) by halting activity of metalloproteinase and disintegrin with throbospondin-type-5. The efficacy of extract along with ellagic acid was determined on destruction of cartilage by giving extract as a constituent of diet of anterior cruciate ligament-transected rats (ACLT). The results suggested that P. guajava leaves extract have role in suppressing progression of OA in ACLT rats and inhibition of joint destruction at early stages through ellagic acid-mediation [70].

1.10. Antidiarrheal Activity

The antidiarrheal effect of P. guajava leaf extract carried out at normal rats and diarrheal rats suggested promising effect. Four groups were formed using normal rats: low-dose P. guajava leaves extract, high dose P. guajava leaves extract, control and gallic acid while 5 groups were formed using diarrheal rats: low-dose P. guajava leaves extract, high-dose P. guajava leaves extract, desmopressin, untreated control group and gallic acid. The low-dose P. guajava extract was equal to 50 mg/kg, high-dose P. guajava extract was equal to 100 mg/kg for both normal and diarrheal rats while desmopressin was used 0.2 mg/kg for a period of one month. The administration of P. guajava leaves extract to diarrheal rats stabilized all the parameters such as kidney weight decline, levels of potassium, sodium and chloride in serum, urine volume, serum urea etc. along with antidiarrheal effect P. guajava leaves extracts also aids in protein conservation [71]. According to survey, there is no single clinical trial found on intake of guava as active anti-diarrheal ingredient.

1.11. Antiestrogenic Activity

The Guajadial, meroterpenoids, from P. guajava leaves extract reported to have antiproliferative and antiestrogenic activity, the action mechanism is similar to tamoxifen which indicates it as promising therapeutic agent based on phytoestrogen. The enriched fraction of guajadial form crude P. guajava leaves extract has selectivity and antiproliferative activity in vitro against human breast cancer cell lines MCF-7 and MCF-7 BUS. The total growth inhibition for MCF-7 was 5.59 µg/mL and for MCF-7 BUS was 2.27 µg/mL. The in vivo analysis on uterus of pre-pubescent rats also confirmed the antiestrogenic activity as guajadial fraction halted the proliferative activity of estradiol [72].

1.12. Anticancer Potential

1.12.1. Anticancer Activity of Leaves Extract

The ethanolic extract of P. guajava leaves and quercetin isolated fractions reduce CCl4-induced cytotoxic effect on HepG2 cell lines. The levels of GSH, viability and cytotoxicity were reduced in CCl4 treated cell lines while lipid peroxidation, Lactate dehydrogenase (LDH), Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were increased. The levels of all these parameters were regulated in a positive manner through the application of P. guajava leaves extract [73].

1.12.2. Cytotoxic Effect of P. guajava Fruit Extract

With the useful biological effects, it is necessary to determine the cytotoxicity of any drug, formulation and nutraceutical. The P. guajava extract administered orally at 2000 mg/kg and 5000 mg/kg b.w of mice did not make any noticeable change in number of kidney podocyte, liver hepatocyte and body weight. The extract from P. guajava leaves extract is safe to use as it non-toxic to both kidney and liver [74]. The aqueous extract of P. guajava leaves in the diet of Oreochromis niloticus not only increased body weight but also increased the villi surface area by increasing its length and width. The immune response and antioxidant activity were improved as total protein content (glutathione S-transferase, superoxide dismutase, and glutathione peroxidase) increased. The Aeromonas hydrophila, a pathogen towards O. niloticus, inhibited by the presence of P. guajava leaves extract, while the absence of extract in the diet of fish increased the mortality rate [75]. In 2019 Babatola et al. also evaluated the toxicity of aqueous leaves extract of three different species of guava i.e., pink, red and white. The rats were used as test animals for this study and extract was administered at a dose of 50, 500 and 5000 mg/kg bodyweight for a period of 14 days. Observation of experimental periods showed effect on parameters accounted and found no toxic effects with a slight increase in body weight but no deaths. The estimated LD50 was found to be 50–5000 mg/kg for these pink, red and white leaves extract of guava [76].

1.13. Antiviral Activity

The antiviral selectivity of P. guajava leaves extract was determined against herpes simplex virus 1 and human immunodeficiency virus, and median cytotoxicity and half-maximal effective concentration were obtained. The EC50 values for HIV-1 strains and HSV-1 were ranged between 0.05 and 3 mg/mL and below 0.2 mg/mL respectively. Antiviral activity of guava extract was found to be based on flavonoid and phenolic contents as HPLC analysis results revealed the presence of phenols (0.8 to 2.1 GAE mg/mL) and flavonoids (62.7 to 182.1 Rutin Eq mg/g DW) [77]. Some direct studies on P. guajava isolated compounds quercetin, catechin, and gallic acid have antiviral activity against Dengue virus. The catechin is best among the three of them as it showed 100% inhibition (pre-treatment) and 91.8% inhibition (post-treatment) depending upon the experimental strategies [78].

1.14. Antibacterial Activity

In 2019, a study conducted by E. A. J. Silva and his colleagues evaluated antibacterial activity for essential oil present in P. guajava leaves. The essential oil has shown moderate activity for various genus of Streptococcus. The activity was described in terms of MIC values S. sobrinus has MIC value of 100 µg/mL, S. mitis has MIC value of 200 µg/mL, S. mutans has MIC value of 200 µg/mL), S. salivarius has MIC value of 200 µg/mL and sanguinis has MIC value of 400 µg/mL [61]. The crude extracts obtained from P. guajava leaves were evaluated for antimicrobial activities by Priscilla Alexander et al. 2019 have evaluated the antimicrobial activities. Crude extractions have mixed fraction of saponins, flavonoids, tannins, glycosides, terpenoids and steroids. The antimicrobial screening showed that crude extracts were strongly active against S. faecalis, E. coli and S. aureus having MIC value of 5.00 mg/mL. In contrast, ethanolic extracts were more actively involved in inhibition and mean zone values were found out to be 6.72 ± 0.01 for S. faecalis and 10.44 ± 0.02 for E. coli [79]. P. guajava have also been tested for its antibacterial activity as a toothpaste. Three different formulations (F) were made F1, F2 and F3 having leaves powder of P. guajava 10, 15 and 20 mg respectively. Therefore, results revealed that the antimicrobial potential against Streptococcus mutants, Streptococcus oralis, Proteus vulgaris, Bacillus subtilis and Staphylococcus aureus strains concentration dependent and F3 formulation found best one. Among all bacterial strains, the best inhibition found for Proteus vulgaris i.e., 1.1 cm while lowest zone inhibition was found against Staphylococcus aureus i.e., 0.5 cm [28].

1.15. Acute and Sub-Acute Toxicity of P. guajava Leaves Extract

The acute and subacute toxicity level of P. guajava bark extract was evaluated using Wistar rats. The extract was proved non-toxic and non-lethal and estimated LD50 was found to be >5000 mg/kg body weight for acute toxicity. The variations in relative weight of organs, body weight and other biochemical parameters that were significant were taken into account in treated animals and control group. Single dose administration at 5000 mg/kg body weight is non-toxic while repeated administration at 1000 mg/kg body weight produced sex-specific toxic effect i.e., minor liver inflammation was observed in females. Hence Psidium plant proved to have mild organ toxicity but have hepatoprotective and hematological potency [82].

1.16. Antimicrobial Activity of Essential Oils of P. guajava Leaves

The essential oils present in leaves of P. guajava have known to have cytotoxic and antimicrobial activities. Their antimicrobial activity was determined against three Gram-positive (Streptococcus aureus, Enterococcus faecalis and Staphylococcus aureus) and three Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa and Haemophilus influenzae). The antimicrobial activity of oil was significant against both Gram-positive and Gram-negative strains and ranges between 0–13 mm while no cytotoxicity was observed using brine shrimp lethality bioassay [83]. The essential oil reportedly inhibit two bacterial human pathogens with MIC values that range from 0.065–0.261 mg/mL while it also inhibits some pathogenic fungi in plants i.e., 82.80% inhibition of Fusarium chlamydosporum and 86.02% inhibition of Curvularia lunata [34].

1.17. P. guajava Leaves Activity against Diarrhea

An antidiarrheal activity of P. guajava leaves was clinically measured and three different doses (6-leaf, 10-leaf, and 14-leaf) of P. guajava leaves decoction extracts were used to their ability against diarrhea. The 14-leaf (7.4 g) decoction proved to be the most successful in the testing. Patients who received the decoction three times per day were able to return to normalcy in 72 h as opposed to 120 h for controls. Haemoglobin, liver, and kidney indicators were all within normal limits, which demonstrated the intervention’s safety [84].

2. Industrial Applications of P. guajava

Dyes and pigments are used in numerous industries worldwide, although the discharge of these materials presents significant risks to the natural environment. Nowadays, water contamination is one of the main causes of environmental pollution. Different synthetic dyes are released directly into natural water resources that are potentially pollutant the resources and make it unfit for domestic and agricultural use. On the other hand, the aromatic structures of these dyes give them greater stability and their degradation process is very slow. Further their oxidation through different oxidizing agents is not easy. Thus, these materials become main pollutants to environments. So, there is a crucial need to find environmentally friendly and cost-effective materials and methods to remove these materials from environment. P. guajava L. leaves nanocomposites materials were widely studies for decontamination of these pollutants. In a recent study a silver: iron oxide (α-Fe2O3-Ag) nanocomposite was prepared for decontamination of chromium (VI) ions from water. Further it is observed that the Cr(VI) adsorption on Fe2O3-Ag surface is endothermic and spontaneous in nature. The adsorbed Cr(VI) can easily be recovered (α-Fe2O3-Ag) nanocomposite and used up to five times [85]. In another study P. guajava leaves were used as biosorbents for the removal of Brilliant Green (BG) [86]. Magnetic nanohybrid composite γ-Fe2O3@GL was prepared by incorporated the Maghemite nanoparticles into framework of P. guajava leaves. γ-Fe2O3@GL was developed for water purification and found efficient for adsorption of methylene blue [87].
Plant-derived proteases are widely used in food and pharmaceutical industries. The upward requirement for biologic-based enzymes, in the food and pharmaceutical industries, has made them an interesting topic for physiologists and biochemists. The existence of two pH optima of P. guajava leaves protease suggests that at least two major proteases are present in it [21]. An environmentally friendly and cost-effective material CuONPs was biosynthesized by using P. guajava L. leaf. It showed potential antibacterial activity against Gram-positive and Gram-negative bacteria. It is non-toxic and exhibited good photocatalytic degradation for Congo red (CR) and methylene blue (MB). The SnO2 nanoparticles within the size of 8 to 8 nm were synthesized by using P. guajava L. leaves extract. These nanoparticles photocatalytic activity was analyzed and found effective for photo degradation of reactive yellow 186. A novel, eco-friendly cotton gauze fabric was synthesized by using P. guajava leaves powder extract. The outer membrane of Biocompatible microcapsules was synthesized from P. guajava leaves powder extract, starch core and calcium-alginate (Ca-alginate). This product was found effective for medical uses. Another novel, eco-friendly and cost-effective material, tungsten oxide nanorods (WO3 NRs), was synthesized by using P. guajava leaves extract. These nanorods were found prodigious in photocatalytic degradation of reactive green 19 (RG 19) dye.

This entry is adapted from the peer-reviewed paper 10.3390/molecules27207016

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