Pharmacology of Bergenia pacumbis: History
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Bergenia pacumbis  (Buch.-Ham. ex D.Don) CYWu & JTPan (sinónimo:  Bergenia ligulate  Engl.), es una importante planta medicinal perteneciente a la familia Saxifragaceae, y no debe confundirse con  Bergenia ciliata  (Haw.) Sternb. , y se conoce popularmente como Pashanbheda (que significa disolver el cálculo renal). 

  • Bergenia ligulata
  • antibacterial activity
  • diuretic activity

1. Farmacología

Debido a la presencia de una amplia gama de fitoquímicos,  B. pacumbis  muestra numerosas actividades farmacológicas. Hasta la fecha, una amplia gama de actividades farmacológicas como antiinflamatorio, antibacteriano, antiviral, diurético, antilítico, antibradiquinina, hepatoprotector, antipirético, actividad de α-glucosidasa, eliminación de radicales libres, analgésico, antioxaluria, anti- Se han informado actividades tumorales y cardioprotectoras de varias partes de  B. pacumbis  [ 3 , 18 , 19 , 21 , 22 , 42 ] ( Figura 1 ).
Figura 1.  Aplicaciones farmacológicas críticas de  Bergenia pacumbis  (Buch.-Ham. ex D.Don) CYWu & JTPan.

2. Antiinflamatorio

Los estudios han revelado que los extractos acuosos y alcohólicos de rizomas frescos de  B. pacumbis  muestran actividad antiinflamatoria en sistemas biológicos a un nivel de dosis de 1 g/kg. [ 64 ]. Se inyectó una cantidad de 0,1 ml de solución de carragenina al 1% en la pata izquierda de la rata y provocó un aumento del volumen de la pata de la rata. Este incremento de volumen se mide cada hora y luego se calcula el percentil de inhibición. Los resultados muestran que  B. pacumbis  tiene un excelente potencial para la actividad antiinflamatoria [ 64 , 65 ]. La investigación también ha revelado que  B. pacumbis  posee cierta actividad de eliminación de radicales [ 66 ].

3. Antibacteriano

The literature revealed that B. pacumbis extracts also possess antibacterial activity [3,21,64,67]. The plant extract was used in three concentrations (10, 25, 50 mg/mL), and the antibacterial activity was measured via the disc diffusion method. The various extracts of the plant (methanolic, ethanolic, and aqueous) was tested in a culture plate containing Escherichia coli, Bacillus subtilis, and Staphylococcus aureus at the dosages mentioned above and the extracts contain significant antibacterial activities. Reports show that at a concentration of 50 mg/mL, the antibacterial activity reached maximum levels, which were found to be equal to the antibacterial activity of ciprofloxacin (25 mg/mL) [64].

4. Anti-Viral

Anti-viral activities of B. pacumbis have been reported in a study on Nepalese medicinal plants [35,36]. The extracts (methanolic and hydromethanolic) were analyzed for influenza and herpes viruses, and the highest anti-influenza viral activity was observed at the dosage of 10 μg/mL [68]. The rhizome of B. pacumbis was used to prepare an extract containing methanol and water as a solvent, and this extract had good viral inhibitory properties against the influenza virus [21,68]. The extract inhibits the viral RNA synthesis, and the study shows that the peptide synthesis rate was decreased strongly at the concentration of 10 μg/mL. The study revealed that tannin is the main component present in the plant rhizome extract, increasing protein availability and acting as an antioxidant and as a metal ion chelator in the chosen biological systems [22].

5. Diuretic Activity

The ethanolic extracts of B. pacumbis roots were tested on albino rats to study their diuretic activity using the Lipschit method [13,69]. Diuretic activity was suspected by measuring the volume of urine collected at an interval of 5 h and also by measuring the Na+, K+, and Cl ion concentrations in urine collected from the rats [70]. The ethanol extracts possess the highest diuretic activity. The same group of researchers also studied the effects of an ethanolic extract of B. pacumbis roots on artificial urine and human urine where CaC2O4 crystals were introduced in the first one. In the case of human urine, the crystals were already present. On adding extract prepared from the roots of B. pacumbis, artificial urine showed the reduction of the crystal ring size, which confirms that the extract may be active in-vitro. Nevertheless, when the extract was applied to the human urine, it showed remarkably other characteristics than CaC2O4 crystal inhibition such as antioxidant effects and hypermagneseuric effects. From these results, it was concluded that B. pacumbis possesses diuretic activity [64,69,70].
Further studies revealed that methanolic extracts of B. pacumbis and bergenin showed a noticeable dissolution of urinary calculi in the kidney. In-vitro antilithiatic/anti calcification potential of different extracts obtained from B. pacumbis and Dolichos biflorus L. were tested independently and in combination by the homogeneous precipitation method [33]. The results of tested extracts were compared against ‘Cystone’ (a Himalaya company formulation sold in India) aqueous extract. Bergenia pacumbis extract showed lesser activity while D. biflorus extract displayed almost equivalent activity as compared to ‘Cystone’. Although, the combination of two extracts is less active in comparison to the individual extracts. The author concluded that active constituent/s may act by inhibiting calcium and phosphate accumulation and are non-protein and non-tannin in nature. Another study on rats revealed that, the low doses of B. pacumbis alcoholic extracts (0.5 mg/kg) promote diuresis, but higher doses (100 mg/kg) retard the diuresis produced by urea and urine output. It is also reported that, the aqueous extracts of B. pacumbis have better potential as compared to the aqueous extract of Tribulus terrestris L. for inhibiting the growth of calcium oxalate monohydrate crystals [32]. This study showed that there are secondary metabolites present in B. pacumbis known to play a significant role in the dissolution of calcium oxalate monohydrate crystals [33].

6. Antilithic

The antilithic property of an alcoholic extract of B. pacumbis showed no effect in rats in the inhibition of stone formation, but the low dosage of crude alcoholic extract (0.5 mg/kg of extract) endorses the diuresis, and higher dosage (100 mg/kg of extract) reduced the diuresis produced by urea [71,72]. The study also revealed that applying 0.75% ethylene glycol in water (5–10 mg/kg extract) of B. pacumbis rhizome in rats prevents the deposition of the crystal in the renal tubules of a rat. The application of B. pacumbis rhizome extract prevented the side effects after lithogenic treatment such as polyuria, decreased antioxidant, weight loss, renal dysfunction, etc. The study also showed that after extract application, there was a slight increase in the Mg2+ ions in the urine, indicating the anti-urolithic activity of B. pacumbis [28,29,34,54,71].

7. Anti-Bradykinin Activity

Though the rhizome extract of B. pacumbis shows anti-bradykinin potential, it does not affect the activity of acetylcholine and 5-hydroxytryptamine (5-HT) on guinea-pig ileum. The rhizome extract increases the adrenaline level on the guinea pig trachea, and in addition, the smooth ileum muscle shows cardiotoxicity and central nervous system depressant activity. In rats, the lethal dosage of the aqueous extract of B. pacumbis rhizome was 650 mg/kg (i.p.). It is widely used to treat painful or difficult urination, renal failure, infection, or inflammation of the urinary bladder and crystalluria, which is caused due to the side effects of sulfonamides and penicillin, abscesses, cutaneous infection, dysentery, and diarrhoea [3,17,61].

8. Hepatoprotective

The hepatoprotective activity was investigated in albino rats (weight 25–35 gm) by using the ethanolic extract of B. pacumbis roots and compared with the standard drug “Liv-52” (manufactured by Himalaya Drug Company, Bangalore), by inducing hepatotoxicity using carbon tetrachloride (CCl4). The investigation was performed using the Up and Down or Staircase method [70]. The ethanolic extract of B. pacumbis restored the integrity of hepatocytes indicated by improvement in physiological parameters, which was confirmed by measuring the levels of transaminase, serum alkaline phosphatase, oxaloacetate, serum glutamate, pyruvate transaminase, serum glutamate, and bilirubin levels and known to have a significant hepatoprotective potential [3,13].

9. Antipyretic

The literature revealed that B. pacumbis possess a substantial antipyretic potential. Singh and coworker examined the ethanol (95%) and aqueous extract obtained from the roots of B. pacumbis for their antipyretic potential. The extracts were mixed with 2% gum acacia and injected to Wistar rats (500 and 300 mg/kg body weight) infected with pyrexia [70]. Paracetamol (200 mg/kg, standard antipyretic) was used as a positive control. The rectal temperature of the infected rats was noted after an interval of 1 h. A noteworthy lowering in the rat’s body temperature was noted with ethanol extract (500 mg/kg) (Figure 2). The present study along with others reports validated that B. pacumbis owns substantial antipyretic activity [13,70,73].
Figure 2. Antipyretic activity of Bergenia pacumbis (Buch.-Ham. ex D.Don) C.Y.Wu & J.T.Pan.

10. α-Glucosidase Inhibition Activity

The ethanolic extract (80%) of B. pacumbis rhizome led to the investigation of α-glucosidase activity at dose levels of 5.0, 0.5, and 0.05 mg/mL and the ethyl acetate extract was used to inhibit the effect of α-glucosidase activity. The trigger compound was identified as (+)-afzelechin (2 g), which was confirmed by EI-MS, IR, proton NMR, and 13C NMR spectral analysis [29]. Further, the inhibitory activity of the compound at a concentration of 0.25 mM was studied at a 50% inhibition dose, i.e., 0.13 mm. ID50 values of (+)-catechin and (-)-epicatechin were 12.8 mM and 0.18 mM, respectively. From these data, the α-glucosidase inhibitor in B. pacumbis is primarily due to the presence of (+)-afzelechin [20,29,37].

11. Antioxidant Activity

Bergenia pacumbis methanolic extract efficiently scavenge 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and exhibit good free radical scavenging potential with an IC50 value of 50 µg/mL. The water and n-butanol fractions obtained from methanol extract were screened for their free radical scavenging potential (in-vitro) by DPPH and the nitric oxide assay. The n-butanol and water fractions showed the IC50 value of 4.5 µg/mL and 30 µg/mL, respectively [48,74]. Bergenin isolated from B. pacumbis also showed significant antioxidant potential [59,75].

12. Analgesic

The analgesic potential of B. pacumbis rhizomes was assessed by employing hot plate and tail clip methods using hydroalcoholic extract (250 mg/kg), which was administered intra-gastrically in the mouse. However, the extract exhibited much less analgesic potential during the study [3,13,22].

13. Anti-Oxaluria

Anti-oxaluria activity on Indian adults was studied where tablets were prepared with Didymocarpus pedicellatus R.Br., B. pacumbis, Rubia cordifolia L., Cyperus scariosus R.Br., Achyranthes aspera L., Veronica cinerea Boiss. & Balansa, Hajrul yahood bhasma, and Shilajeet purified in the ratio 65:49:16:16:16:16:16:13 (in mg) and investigated on 32 healthy volunteers and 48 people suffering from stones. All patients were given two tablets (3 times/day) and advised to avoid oxalate-rich foods in their diet, and the treatment lasted for 8 weeks. A steady decrease in oxalate elimination was noted in persons infected with kidney stones, but the level of oxalate elimination was not as low as observed in usual adults. This study revealed that the present formulation might deliver a capable drug that regulate the activity of oxaluria [3,76].

14. Anti-Tumor

Bergenia pacumbis hydroalcoholic extract was injected intraperitoneally in rats to evaluate its anti-tumour potential. The extract exhibited activity against SARCOMA WM1256 IM cell culture at the dose of 20 mcg/mL, which pointed out that B. pacumbis hydroalcoholic extract exhibited cytotoxic activity [3].

15. Cardioprotective

The hypotensive activity of B. pacumbis hydroalcoholic extract was carried out in different animal models. A positive hypotensive activity was noted in dogs when injected with 50 mg/kg dose (i.v.) [3]. Further, the B. pacumbis extract also showed positive inotropic and chronotropic effects on a frog’s heart [17]. While in the case of continuous rabbit’s heart perfusions, the extracts exhibited adverse chronotropic and inotropic effects with a decrease in coronary flow. The alcoholic extract B. pacumbis elicited marked anti-bradykinin activity (in-vitro and in-vivo) but was unable to modify the response of acetylcholine and 5-HT on guinea-pig isolated ileum [3,77].

16. Insecticidal Activity

Kashima y colaboradores evaluaron el potencial insecticida del aceite esencial y el ácido parasórbico obtenidos de las raíces de  B. pacumbis  contra adultos de  Drosophila melanogaster . Los resultados revelaron que tanto el aceite esencial como el ácido parasórbico eran activos contra el insecto, pero el ácido parasórbico tenía más potencial insecticida en comparación con el aceite esencial [ 20 ].

This entry is adapted from the peer-reviewed paper 10.3390/plants11091129

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