In vitro and In vivo Study of Gastroprotective effect of Purified Extract Andrographis paniculata

 

Jastria Pusmarani¹*, Citra Dewi², Risky Juliansyah Putri², Nur Hatidjah Awaliyah Halid²,

Sasri Intan Febriani³, Febrianti Husni³, Setyo Purwono⁴, Zullies Ikawati⁵

¹Department of Pharmacology and Clinical Pharmacy of Universitas Mandala Waluya, Kendari, Indonesia.

²Department of Phytochemical of Universitas Mandala Waluya, Kendari, Indonesia.

³Department of Pharmacy of Universitas Mandala Waluya, Kendari, Indonesia.

⁴Department of Pharmacology and Therapy of Universitas Gadjah Mada, Yogyakarta, Indonesia.

⁵Department of Pharmacology and Clinical Pharmacy of Universitas Gadjah Mada, Yogyakarta, Indonesia.

 

ABSTRACT:

Gastric ulcers are caused by excessive gastric acid secretion, alcohol, and long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin is one of the NSAIDS that can induce peptic ulcers. Traditional medicines that have been proven to have gastroprotective activity is Andrographis paniculata (APAC). The purpose of this study is to assess the antioxidant activity and gastroprotective effect of purified extract of APAC. The herbal treatment was given for 7 days, and on the eighth day, all groups except the negative control (Na CMC 0.5%) were given 1000mg/kgBW of aspirin. Six hours later, the rats were sacrificed and opened for macroscopic examination, pH gastric juice value, the volume of gastric value, ulcer index, and inhibition percentage. Antioxidant studies using 2,2-diphenyl-1-picrylhydrazyl (DPPH) showed that APAC has strong antioxidant activity with IC₅₀ value = 64.54. APAC could reduce the occurrence of gastric ulcers by decreasing gastric pH, ulcer index, and increasing inhibition percentage (P=0.000<0.05). Andrographis paniculata has gastroprotective properties associated with antioxidant activity.

 

 

 

INTRODUCTION: 

Peptic ulcer disease (PUD) is a complication caused by imbalance between aggressive agents (e.g., acid and pepsin), and protective factors (e.g., mucin, bicarbonate, prostaglandin, nitric oxide, and growth factors) in the gastro-intestinal tract (GIT)^1,2,3,4. Peptic ulcers or gastric ulcers affect at least 10% of the world population⁵. Symptoms of gastric ulcer can include dyspepsia, nausea, vomiting, bloating stomach, heart burn, burping, and a full stomach. PUD also has been linked to a higher mortality rate in patients suffering from gastric and duodenal ulcers^6,7. Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause peptic ulcers, and aspirin has been linked to up to a 20% increase in gastric mucosal damage caused by long-term NSAID therapy^6,8.

 

In Indonesia, medicinal plants such as Andrographis paniculata (APAC) were used empirically to treat gastric ulcers. It is also known as the "King of Bitters." Andrographis paniculata thrives in Asia, such as China, Thailand, India, Sri Lanka, and Pakistan⁹.

 

Andrographis paniculata has several activities, such as anti-angiogenic activity, anti-inflammatory and antiproliferative in vitro, hepatoprotective effect, neuroprotective effect, antibacterial activity, gastroprotective effect, antidiabetic, antihyperlipidemia effect, anticancer, antioxidant and antimicrobial activity¹⁰-²⁴. It is a well-known medicinal plant for the treatment of gastric problems¹. The presence of pure compounds, specifically andrographolide, was demonstrated in phytochemical reports from Andrographis paniculata. Andrographolide can prevent ulcers because it has antisecretory and  gastroprotective activity, reducing the occurrence of ulcers, lowering the acidity of gastric juices, lowering the ulcer index, increasing PGE-2 levels in the stomach, and decreasing the activity of pepsin and H⁺K⁺ATPase (proton pump) enzymes^1,17,25.

 

Purification of crude extract can yield andrographolide compounds with gastroprotective properties from Andrographis paniculata. The purpose of extract purification is to remove certain chemical compounds, and to eliminate impurity components such as fat, chlorophyll, and others. Purification also aims to obtain pure natural components free of unnecessary chemical components that can be efficiently administered when testing in vivo gastroprotective activity and in vitro antioxidant activity. The study aims to determine antioxidant activity and gastroprotective effect of purified extract of Andrographis paniculata.

 

MATERIALS AND METHODS:

Materials:

The tools used are a stirring rod, glass beaker (Pyrex^®), separating funnel (Pyrex^®), Erlenmeyer (Pyrex^®), measuring cup (Pyrex^®), filter paper, spatula, dropper, aluminium foil, oven, analytical balance, rotary evaporator R-144 Buchi with the Buchi B-169 vacuum system, UV-Visible spectrophotometer (Shimadzu^®), rotary evaporator (Buchi^®) with the vacuum system (Buchi^®), digital Callipers, pH meter, burner funnel (Pyrex^®).

 

Sample Andrographis paniculata was obtained from Yogyakarta. Sucralfate, a cytoprotective agent indicated for gastric ulcers, was obtained from PT Fahrenheit Tbk, Indonesia. Aspirin (inducer for gastric ulcers). Chemical and reagens-methanol, aquadest, ethanol, n-hexane, dan Ethyl acetate.

 

Preparation of Purified extract of Andrographis paniculata:

The Viscous ethanol extract of Andrographis paniculata was purified by adding n-hexane and shaking until the colour of the solvent become green (this solvent is removed). The insoluble fraction of n-hexane was re-purified by adding ethyl acetate and agitating it until the brown color of the solvent was removed.The insoluble fraction of ethyl acetate contained the flavonoid and lactones diterpenoids (including Andrographolide). The ethyl acetate insoluble fraction was collected and evaporated under reduced pressure to produce a viscous extract known as purified extract²⁶.

 

In Vitro Study: Antioxidant activity using DPPH free radical scavenging activity:

The radical scavenging capacity of purified extract Andrographis paniculata was determined using DPPH radicals. 4ml of DPPH 0.0001 M solution and 50 ml of sample solution were vortexed for 1 minute and left to stand for 10 minutes. The absorbance is measured at a wavelength of 517nm, and the DPPH absorbance readings are 0.0001M. The percentage of DPPH radical attenuation was calculated and plotted on the linear regression curve, as well as the IC₅₀ value.

 

In Vivo Study: Gastroprotective Effect of purified extract of Andrographis paniculate:

Animals:

We used male Wistar rats (2-3 month old) weighing 150-200g. The rats were obtained from Jember Regency, East Java. The rats were kept in a cage at a constant temperature (24-270°C) and relative humidity (50-70%) with controlled light (12 hours light/dark). All animals were fed standard laboratory diets and water ad libitum. The animals were acclimatized and quarantined for at least two weeks before experiment.

 

Animals Experimental:

The doses of purified extract of Andrographis paniculata (APAC) were 450mg/kgBW, 550 mg/kgBW and 650mg/kgBW. The animals were randomly devided into six groups of five rats each. Group 1 was negative controls rats that received suspension of NaCMC 0.5%. Group 2 was positive controls rats (sucralfat 120mg/5 ml). Group 3 was induced controls rats (Aspirin 1000 mg/kgBB). Group 4 was treatment group rats with 450 mg/kgBW purified extract of Andrographis paniculata 450mg/kgBW. Group 5 was treatment group rats with 550mg/kgBW purified extract of Andrographis paniculata 550mg/kgBW. Group 6 was treatment group rats with 650mg/kgBW purified exract of Andrographis paniculata 650mg/kgBW.

 

Table 1: Number of scoring lesion formed of gastric

Number of Scoring	Number of lesions (mm)
1	< 1
2	1.00 -2.00
3	2.01-3.00
4	3.01-4.00
5	4.01-5.00
10	>5.00
Perforation	>25

 

Groups 1, 2, 3, 4, 5 and 6 were given oral treatment for 7 days. On the seventh day, all animals were fasted for 18 hours. Group 3 was given 0.5% NaCMC orally for seven days. On the eighth day, all animals were given aspirin 1000mg/kg BW except for group 1. After 6 hours of aspirin treatment, the rats were sacrificed by cervical dislocation. The rats were dissected, and their stomachs were removed and opened for macroscopic examination by measuring the gastric pH, volume of stomach, and counting the lesions formed with digital calipers^27,28. The lesions formed were scored and the results are shown in table 1²⁹.

 

The ulcer index (mm) for each group was determined by the earlier method described by Cho and Olge³⁰. Inhibition percentage calculated with the following formula:

                                       Total of Ulcer score

Ulcer Index (UI) = -----------------------------

                                Total of ulcerated rats

 

           IU (Induced Group) - IU (treated group)

% Inhibition = ------------------------------------------- x 100%

IU (Induced Group)

 

Microscopic Histopathological Examination:

The method examination histopathogical of stomach was described by Drury and Wallington for estimating histological assessment of the stomach tissue³¹. The histological of the stomach rats were observed necrotic change, oedema and inflammatory cell infiltration to determine all stomach of rats group^32,33.

 

RESULT:

Phytochemical Analysis:

Purified extract of APAC was initially investigated for phytochemical screening as part of the phytochemical qualitative analysis. The results show a positive reaction to alkaloid, flavonoid, saponin, and triterpenoid content (Table 2).

 

 

In vitro Study: Antioxidant activity using DPPH free radical scavenging activity:

Antioxidant activity of purified extract of APAC were determined using 2,2-diphenyl-1-picrilhydrayl (DPPH) as a reagent and plant purified extract. DPPH free radical scavenging assay of the vitamin C and purified extract of APAC expressed by IC₅₀ value (Table 3). The IC₅₀ value of purified extract of APAC is 50-100ppm, indicating that it has strong antioxidant activity.

 

In Vivo Study: Gastroprotective Effect of purified extract of Andrographis paniculate:

Purified extract of APAC treatment results in a lower ulcer index in an aspirin-induced gastric ulcer test on rats. Except for the purified extract of APAC 450 mg/kgBW groups, no gastric ulcers were found in the purified extract of APAC 550mg/kgBW and purified extract of APAC 650mg/kgBW treatment groups. Gastric ulcers were decreased in the purified extract of APAC 550mg/kgBW and purified extract of APAC 650 mg/kgBW groups with a greater than 100% inhibition value than in the aspirin-induced gastric ulcers groups (Table 4).

 

Table 2: Results of the Phytochemical Qualitative Analysis of purified extract of andrographis paniculata

*Plus (+) is indicates the presence and minus (-) is absence

 

Table 3: Radical scavenging activities of purified extract of Andrographis paniculate

Sample	Concentration (ppm)	% Inhibition	IC50 (µg/mL)
APAC	200	52.42	81.93
	300	55.65
	400	60.22
	500	61.56
	600	62.90
Vitamin C	2	4.30	5.515
	3	5.11
	4	5.91
	5	6.45
	6	7.26

 

Table 4: Gastroprotective acitivities of purified extract of Andrographis paniculata

Animal group	Pre treatement Group	pH gastric  (Mean ± SD)	Volume of gastric (Mean ± SD)	Scoring of ulcers  (Mean ± SD)	Ulcer Index	% Inhibition
1	Na CMC 0.5% (Negative group)	4.34±0.73	1.42±0.48	1.0±0.00	0	-
2	Sucralfat (120 mg/5 ml)	4.67±0.56	1.18±0.64	1.0±0.00	0	100
3	Aspirin (1000 mg/kgBW)	5.21±0.30	4.48±0.59	10±0.00	10	0
4	Purified extract of APAC 450 mg/kgBW	5.39 ± 0.59*	6.12 ± 1.49*	1.00 ± 0.00*	2.66	65
5	Purified extract of APAC 550 mg/kgBW	5.48 ± 0.68*	3.12 ± 1.29*	1.00 ± 0.00*	0	100
6	Purified extract of APAC 650 mg/kgBW	5.39±0.50*	3.29 ± 1.30*	1.00 ± 0.00*	0	100

*P=0.000<0.05-One Way ANOVA test showed significant difference to prevent gastric ulcers in APAC 450 mg/kgBW, APAC 550 mg/kgBW and APAC 650 mg/kgBW group

 

 

Figure 1: Macroscopic physical of the gastric mucosa (→) in rats treated with; (1) Group Na CMC; (2) Group sucralfat (120mg/5 ml); (3) Group Aspirin (1000 mg/kgBW); (4) Group purified extract of APAC (450 mg/kgBW); (5) Group purified extract of APAC (550 mg/kgBW); (6) Group purified extract of APAC (650 mg/kgBW)

 

The results of experimental value were stated as mean± standard deviation (SD). One-way analysis of variance (ANOVA) was used to compare different groups. P<0.05 indicated a significant difference, and each group was compared using the LSD test. In this study, the purified extract of APAC ANOVA test value from ulcer scoring is 0.000 (P<0.05), indicating that the plant has gastroprotective activity (Table 4).

 

Macroscopic physical of the gastric mucosa of rats treated by purified extract of APAC is not found ulcer, except for group purified extract of APAC 450 mg/kgBW and group aspirin (Figure 1).

 

Histopathological of the gastric mucosa of rats treated by purified extract of APAP is not found necrosis ulcerative bleeding or oedema in tunica mucosa-submucosa in group APAC except for group APAC 450 mg/kgBW and group aspirin (Figure 2). In our study, histopathological examination revealed that ulcer control pre-treatment with Na CMC (negative control group) caused significant damage to the gastric mucosa, including necrosis in the tunica mucosa and submucosa, oedema in the submucosa, plasma cell infiltration, and lymphocyte in the tunica mucosa and submucosa (Figure 1). Purified extract of APAC 450mg/kgBW is displayed histological changes such as oedema in submucosa, plasma cell infiltration and lymphocyte in the tunica mucosa and submucosa. Purified extract of APAC 550 mg/kgBW as well as purified extract of APAC 650 mg/kgBW groups, protects the gastric mucosa better, as evidenced not specifical pathologic changes and no oedema with infiltration in plasma cell. The gastric mucosa was protected by purified extract of APAC with no necrosis, oedema, or infiltration in the tunica mucosa and submucosa, and showed a similar protective ulcer gastric with sucralfate groups (Figure 2). Aspirin 1000 mg/kgBW administration can cause histological changes in mucosal regions, such as necrosis ulcerative bleeding in tunica mucosa-submucosa, oedema in tunica submucosa with neutrophil infiltration, lymphocyte and plasma cell tunica mucosa and submucosa (Figure 2).

 

Fig. 2: Histopathological of the gastric mucosa (→) in rats treated with; (A) Group Na CMC; (B) Group sucralfate (120mg/5 ml); (C) Group Aspirin (1000 mg/kgBW); (D) Group purified extract of APAC (450 mg/kgBW); (E) Group purified extract of APAC (550 mg/kgBW); (F) Group purified extract of APAC (650 mg/kgBW)

 

DISCUSSION:

In the present study, the gastro-protective activity and antioxidant activity of purified extract of Andrographis paniculata (APAC) was investigated in aspirin-induced gastric-ulceration in rats. Preliminary phytochemical of test purified extract of APAC was support prior to the pharmacological study. Purified extract of APAC was positive for alkaloid, flavonoid, tannins, and terpenoid. Result of this study has documented similar study. Andrographis paniculata roots and Andrographis paniculata leaves have total phenolic, andrographolide and alkaloids content (particularly caffeine, theobromine, theophylline, and indole alkaloids), similar from the results of this study³⁴.

 

In Vitro Study: Antioxidant activity using DPPH free radical scavenging activity:

Antioxidant activity of purified extract of APAC was determined by DPPH free radical scavenging activity. DPPH assay have several advantages include less cost, simple to operated, rapid, reduced reagent consumption and aloft analysis of antioxidant activity³⁵. In vitro, extraction of plants were neutralized by DPPH radical scavenging activity^36,37,38,39. DPPH was a dark-coloured crystalline compound include radical particles that were stable⁴⁰.

 

In this study, purified extract of APAC has antioxidant activity that related inhibition of gastric ulcers induced by aspirin⁴¹. antioxidant defence enzymes are responsible for scavenging reactive oxygen species (ROS) and other free radicals that cause stomach damage. Andrographis paniculata can be potent to scavenge ROS and stimulate endogenous antioxidant enzymes in the stomach⁴².

 

In Vivo Study: Gastroprotective Effect of Andrographis paniculata

Investigation evaluated the effects of purified extract of Andrographis paniculata (APAC) against aspirin-induced gastric ulcer model. Gastric ulcer was induced by oral administration of aspirin (1.000 mg/kgBW). Aspirin, one of the NSAIDs, caused a gastric ulcer due to its anti-inflammatory activity. Inhibition of prostaglandin (PG) and cyclooxygenase (COX) are central of the major anti-inflammatory actions of NSAID. Inhibiting (PG) products (particularly PGE2 and PGI2) reduces blood flow to the inflamed site and reduces oedema. PG has been linked to the cardinal signs of inflammation and plays important roles in a variety of physiological processes. PG plays important role as mediators of mucosal defense and repair in the gastrointestinal (GI) tract. Inhibiting PG synthesis causes GI tissues to be much more damaged by luminal irritants (including gastric acid and bile) and less able to restore mucosal structure and function after injury. NSAIDs induce gastro-duodenal ulceration and bleeding by inhibiting PG synthesis, and other NSAID effects cause damage in the small intestine injury to subclinical patients⁴³.

 

Gastric ulcers were caused by the mechanism of action of NSAID, which can be linked to the inhibition of cyclooxygenase (COX)-1 and COX-2. COX-1 inhibition leads to decreased mucosal flow, mucus and bicarbonate secretion, and impaired platelet aggregation, whereas COX-2 inhibition leads to decreased angiogenesis and increased leukocytes. Aspirin is one of the NSAIDs that inhibits COX-1 more effectively than COX-2^29,44.

 

Gastroprotective effect of purified extract of APAC In addition, the volume gastric juice parameters of rats treated with APAC decreased the gastric volume and increased the pH of gastric juice in the APAC 450 mg/kgBW, APAC 550mg/kgBW, and APAC 650 mg/kgBW groups compared to the aspirin groups. Furthermore, the volume of gastric juice was greater in the APAC 550mg/kgBW and APAC 650 mg/kgBW groups than in the aspirin groups (Table 4). However, gastric ulcer has been demonstrated in the aspirin and APAC 450mg/kgBW groups, but not in the APAC 550 mg/kgBW and APAC 650mg/kgBW groups (

Figure 1).

 

According to previous study that ulcerated animals showed typical histological relate evidenced by erosion of the surface epithelial cells, submucosal oedema, infiltration of inflammatory cells, and thinning of the muscular layer^45,46,47,48. In this study, purified extract of APAC (550 & 650 mg/kgBW) after ulcer induction improved the histopathology mucous layer of ulcerated gastric tissues. The study of Saboriendo et al. evaluated of gastric mucosal tissues of the Andographis paniculata treated in an aspirin-induced showed almost normal, continuous formation of the epithelial layer, re-epithelialization and healing from the ulceration gastric mucosa⁴⁹.

 

This antioxidant effect of Andrographis paniculata has been linked to many of its bioactive molecules. Compounds components of Andrographis paniculata, which is responsible for antioxidant effect include polyphenols, flavonoids, terpenoids, tannins, and andrographolide⁵⁰. APAC contains polyphenols compound that has natural antioxidant with the potential to protect tissue from free radical damage⁵¹.  Polyphenol compounds have gastroprotective properties by suppressing or modulating peptic ulcers induced by Helicobacter pylori⁵². Flavonoid compounds have several mechanisms in the gastroprotective effect, such as anti-secretory, cytoprotective, healing of gastric ulcers and antioxidant agents. Flavonoids were potent reduced histamine secretion from mast cells, inhibit lipid peroxidation, protect the gastric half of mucosal glycoprotein and may enhance in nitric oxide (NO) action⁵³.

 

Purified active fraction of Andrographis paniculata also contains terpenoids, which is consistent with the findings of this study's purified extract of Andrographis paniculata. Terpenoids with anti-ulcerogenic effects are generally cytoprotective, increasing mucus production and prostaglandin (PG) content, repairing gastric mucosal blood flow, and secreting bicarbonate. It was found to improve ulcer healing by lowering lipid peroxide and increasing superoxide dismutase (SOD) activity in the stomach⁵².

Purified extract of APAC has contained tannins compound to present antioxidant activity. It has several experimental mechanisms of gastroprotective effect such as promote tissue repair, exhibit anti Helicobacter pylori effects, and tannin can involve in gastrointestinal tract anti-inflammatory processes. Tannin can protect the stomach from gastric ulcers by forming a tannin-protein complex layer that promotes greater resistance to chemical, irritant, and mechanical injury⁵³.

 

Results of this study that purified extract of APAC has saponins compound. Saponins have been shown to have anti-ulcer activity in a variety of experimental models, most notably through the activation of mucous membrane protective factors⁵⁴. Saponin works primarily through anti-secretory mechanisms, obstructing acid secretion and total acid output while also lowering the pH of gastric juice⁵².

 

Andrographolide of APAC has related with the gastroprotective effect of Andrographis paniculata. According to study of Saranya et al. that andrographolide protect the gastric ulcer by antioxidant, cytoprotective and secretory effects⁵⁵.

 

Other studies have found that the plant can inhibit the activity of gastric mucosal H⁺K⁺-ATPase in vitro, decrease the activity of pepsin and myeloperoxidase enzymes, and maintain the levels of glutathione (GSH) and antioxidant enzymes^21,56.

 

In this research demonstrate that purification extract of Andrographis paniculata (APAC) has protect aspirin-induced gastric mucosal injury by antioxidant effect, cytoprotective defenses and a potential inhibition of H⁺K⁺-ATPase enzyme.

 

CONCLUSION:

Based on the results of this study, we can conclude that purified extract of Andrographis paniculata has a significant gastroprotective effect through antioxidant activity, cytoprotective defenses and a potential inhibition of H⁺K⁺-ATPase enzyme.

 

CONFLICT OF INTEREST:

The authors have no conflict to declare in this report.

 

ACKNOWLEDGMENTS:

The author would like to thank Universitas Mandala Waluya and Universitas Gadjah Mada for providing us with the opportunity to conduct this research. The author would like to thank to Dr. drh. Sitarina, lecturer of pathology, faculty of veterinary medicine, Universitas Gadjah Mada, for helping us in histopathological studies.

 

ETHICAL APPROVALS:

Ethical animals of this research approved by medical faculty of Universitas Gadjah Mada under the serial number KE/FK/108/EC/2019.

 

REFERENCES:

1.      Shoaib A. Siddiqui HH. Siddiqui HH. Antiulcerogenic activity of hydromethanolic extract of Andrographis paniculata in Indomethacin and Indomethacin plus pylorus ligation induced gastric ulcer in rats. 2014;04(39):8-15. doi:10.15272/ajbps.v4i39.635

2.      Prabhu V. Shivani A. An overview of history, pathogenesis and treatment of perforated peptic ulcer disease with evaluation of prognostic scoring in adults. Ann Med Health Sci Res. 2014;4(1):22-29.

3.      Taş İ. Ülger BV. Önder A. Kapan M. Bozdağ Z. Peptik ülser perforasyonunda morbidite ve mortaliteye etkili risk faktörleri. Turkish J Surgery/Ulusal Cerrahi Derg. 2015;31(1).

4.      Nitin M. Girish M. Chetan M. Javed A. Krunal S. Krishna K. Comparative Influence of Selected Antioxidants with Lansoprazole in Aspirin Induced Ulcer Model in Rats. Res J Pharm Technol. 2011;4(8):1273-1277.

5.      Shimoyama AT. Santin JR. Machado ID. et al. Antiulcerogenic activity of chlorogenic acid in different models of gastric ulcer. Naunyn Schmiedebergs Arch Pharmacol. 2013;386(1):5-14.

6.      Thorsen K. Søreide JA. Kvaløy JT. Glomsaker T. Søreide K. Epidemiology of perforated peptic ulcer: age-and gender-adjusted analysis of incidence and mortality. World J Gastroenterol WJG. 2013;19(3):347.

7.      Zhang X. Mo H. Huang Y. risk factor and mortality of peptic ulcer disease. Aliment Pharmacol Ther. 2016;44(4):424-425.

8.      Wallace JL. Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy. World J Gastroenterol WJG. 2013;19(12):1861.

9.      Huidrom S. Deka M. Determination of antioxidant property of Andrographis paniculata. Indian J Drugs Dis. 2012;1:13-18.

10.   Zou W. Xiao Z. Wen X. et al. The anti-inflammatory effect of Andrographis paniculata (Burm. f.) Nees on pelvic inflammatory disease in rats through down-regulation of the NF-κB pathway. BMC Complement Altern Med. 2016;16(1):1-7.

11.   Shaikh U. Meshram RJ. Gacche RN. European Journal of Integrative Medicine An investigation on in vitro anti-in fl ammatory and antiproliferative potential of isolated Labdane diterpenoids from Andrographis paniculata (Burm . f .) wall . Ex nees : An important medicinal plant prescribed . 2019;32(September). doi:10.1016/j.eujim.2019.100983

12.   Vidhya TM. In Vitro Evaluation of Anti-Inflammatory Activity of Andrographis paniculata. Res J Pharm Technol. 2018;11(3):957-958.

13.   Sivaraj A. Vinothkumar P. Sathiyaraj K. Sundaresan S. Devi K. Senthilkumar B. Hepatoprotective potential of Andrographis paniculata aqueous leaf extract on ethanol induced liver toxicity in albino rats. J Appl Pharm Sci. 2011;1(6):24.

14.   Nasir A. Abubakar MG. Shehu RA. Aliyu U. Toge BK. Hepatoprotective effect of the aqueous leaf extract of Andrographis paniculata Nees against carbon tetrachloride–induced hepatotoxicity in rats. Niger J Basic Appl Sci. 2013;21(1):45-54.

15.   Subramaniam S. Khan HBH. Elumalai N. Lakshmi SYS. Hepatoprotective effect of ethanolic extract of whole plant of Andrographis paniculata against CCl 4-induced hepatotoxicity in rats. Comp Clin Path. 2015;24(5):1245-1251.

16.   Gu L. Lu J. Li Q. et al. A network-based analysis of key pharmacological pathways of Andrographis paniculata acting on Alzheimer’s disease and experimental validation. J Ethnopharmacol. 2020;251:112488.

17.   Mishra V. Pandey HP. Kumar Barthwal M. et al. Andrographaloide from Andrographis Pannicuolata Significantly Inhibited the H + K +-ATPase and Increased the PGE2 Level in Rats Full Paper.

18.   Wasman SQ. Mahmood AA. Chua LS. Alshawsh MA. Hamdan S. Antioxidant and Gastroprotective Activities of Andrographis Paniculata (Hempedu Bumi) in Sprague Dawley Rats.  2011; 49.

19.   Nugroho AE. Lindawati NY. Herlyanti K. Widyastuti L. Pramono S. Anti-diabetic effect of a combination of andrographolide-enriched extract of Andrographis paniculata ( Burm f .) Nees and asiaticoside-enriched extract of Centella asiatica L in high fructose-fat fed rats. 2013;51(December):1101-1108.

20.   Liaqat H. Andrographis paniculata: A Review of its Anti-Cancer Potential. Med Aromat Plants (Los Angeles). 2021;10:384.

21.   Mary R. Banu N. Antiquorum sensing potential of andrographolide from Andrographis paniculata in Vibrio harveyi. Res J Pharm Technol. 2017;10(2):449-452.

22.   Deepak S. Pawar A. Shinde P. Study of antioxidant and antimicrobial activities of Andrographis paniculata. Asian J Plant Sci Res. 2014;4(2):31-41.

23.   Tiwari RK. Pandey R. Shukla SS. Tiwari P.  Shah H. Antibacterial Activity of Ariel Part of Andrographis paniculata. Res J Pharmacogn Phytochem. 2014;6(3):122.

24.   Nugroho AE. Rais IR. Setiawan I. et al. Pancreatic effect of andrographolide isolated from Andrographis paniculata (Burm. f.) Nees. Pak J Biol Sci. 2014;17(1):22-31.

25.   Geetha A. Saranya P. A study on the gastroprotective effect of Andrographis paniculata and andrographolide in rats subjected to pylorus ligation. J Pharm Res. 2012;5(2):787-791.

26.   Kaskoos RA. Ahamad J. Evaluation of pharmacognostic features of aerial parts of Andrographis paniculata Wall. J Pharmacogn Phytochem. 2014;3(1).

27.   Mahurkar N. Sayeed Ul. Hasan SM. Synergistic Antiulcer Effect of Melatonin and Esomeprazole Combination in Pylorus Ligation, Ethanol, Aspirin induced Peptic Ulcers. Asian J Pharm Res. 2015;5(1):10-14.

28.   Kadhem MA, Abdul-Niby AA, Khassaf HK. Study the effect of Ethanolic extract of Anethum graveolens L. on Aspirin induced Gastric Ulcer in Male Guinea Pigs. Res J Pharm Technol. 2018;11(9):3793-3798.

29.   Pusmarani J. Ifaya M. Isrul M. Saleh A. Gastroprotective Effect of Lannea coromandelica Stem Bark in Rat induced by Aspirin. Res J Pharm Technol. 2019;12(4):1646-1648.

30.   Cho CH. Ogle CW. Cholinergic-mediated gastric mast cell degranulation with subsequent histamine H1-and H2-receptor activation in stress ulceration in rats. Eur J Pharmacol. 1979;55(1):23-33.

31.   Carleton HM. Drury RAB. Wallington EA. Carleton’s Histological Technique. Oxford University Press, USA; 1980.

32.   Kathirvelu P. Cheriyan BV. Jagan N. Viswanathan S. Kumar SV. Kamalakannan P. Gastroprotective and Antioxidant effect of Petroleum ether Extract of Eupatorium triplinerve Vahl. Res J Pharm Technol. 2019;12(11):5163-5166.

33.   Zaghlool SS. Abo-Seif AA. Rabeh MA. Abdelmohsen UR. Messiha BAS. Gastro-protective and anti-oxidant potential of Althaea officinalis and solanum nigrum on pyloric ligation/indomethacin-induced ulceration in rats. Antioxidants. 2019;8(11):512.

34.   Kurzawa M. Filipiak-Szok A. Kłodzińska E. Szłyk E. Determination of phytochemicals, antioxidant activity and total phenolic content in Andrographis paniculata using chromatographic methods. J Chromatogr B. 2015;995:101-106.

35.   Sirivibulkovit K. Nouanthavong S. Sameenoi Y. Based DPPH assay for antioxidant activity analysis. Anal Sci. 2018;34(7):795-800.

36.   Aini F. Maritsa H. Riany H. Antioxidant activity of nipah endophytic fungi (Nypha fruticans Wurmb) from Tanjung Jabung Timur Jambi. J Biota. 2019;5(2):104-109.

37.   Kurniawan YS. Priyangga KTA. Krisbiantoro PA. Imawan AC. Green chemistry influences in organic synthesis: A review. J Multidiscip Appl Nat Sci. Published online 2021.

38.   Amrulloh H. Fatiqin A. Simanjuntak W. Afriyani H. Annissa A. Bioactivities of nano-scale magnesium oxide prepared using aqueous extract of Moringa oleifera leaves as green agent. Adv Nat Sci Nanosci Nanotechnol. 2021;12(1):15006.

39.   Lalrinzuali K. Vabeiryureilai M. Jagetia GC. Lalawmpuii PC. Free radical scavenging and antioxidant potential of different extracts of Oroxylum indicum in vitro. Adv Biomed Pharm. 2015;2(3):120-130.

40.   Sridhar K. Charles AL. In vitro antioxidant activity of Kyoho grape extracts in DPPH and ABTS assays: Estimation methods for EC50 using advanced statistical programs. Food Chem. 2019;275:41-49.

41.   Mahurkar N. Sayeed ul Hasan SM. Antiulcer activity of Commicarpus Chinensis in ethanol and aspirin induced ulcers. Asian J Pharm Res. 2014;4(3):119-122.

42.   Nartey ET. Ofosuhene M. Agbale CM. Anti-ulcerogenic activity of the root bark extract of the African laburnum “Cassia sieberiana” and its effect on the anti-oxidant defence system in rats. BMC Complement Altern Med. 2012;12(1):1-9.

43.   Iwamoto J. Saito Y. Honda A. Matsuzaki Y. Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy. World J Gastroenterol WJG. 2013;19(11):1673.

44.   Wallace JL. Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself? Physiol Rev. 2008;88(4):1547-1565.

45.   Tanaka T. Morito K. Kinoshita M. et al. Orally Administered Phosphatidic Acids and Lysophosphatidic Acids Ameliorate Aspirin-Induced Stomach Mucosal Injury in Mice. Dig Dis Sci. 2013;58(4):950-958. doi:10.1007/s10620-012-2475-y

46.   Salah Khalil M. The postulated mechanism of the protective effect of ginger on the aspirin induced gastric ulcer: Histological and immunohistochemical studies. Published online 2015.

47.   Majeed W. Aslam B. Javed I. et al. Histopathological evaluation of gastro protective effect of Berberis vulgaris (Zereshk) seeds against aspirin induced ulcer in albino mice. Pak J Pharm Sci. 2015;28(6).

48.   Salga MS. Ali HM. Abdulla MA. Abdelwahab SI. ElhassanTaha MM. Yagoub U. Synthesis and gastroprotective activities of some zinc (II) complexes derived from (E)-2-(1-(2-(piperazin-1-yl) ethylimino) ethyl) phenol and (E)-4-(1-(2-(piperazin-1-yl) ethylimino) ethyl) benzene-1, 3-diol Schiff bases against aspirin induced ulceration. Arab J Chem. 2017;10:S1578-S1589.

49.   Saboriendo SV, Sumalapao DEP, Villarante NR. Therapeutic and prophylactic effect of Andrographis paniculata on aspirin-induced gastric ulcer. Natl J Physiol Pharm Pharmacol. 2017;7(8):781.

50.   Sahu M. Rao SP. Review literature: Andrographis paniculata. Res J Pharmacol Pharmacodyn. 2018;10(4):166-170.

51.   de Lira Mota KS. Dias GEN. Pinto MEF. et al. Flavonoids with gastroprotective activity. Molecules. 2009;14(3):979-1012.

52.   Awaad AS. El-meligy RM. Soliman GA. Natural products in treatment of ulcerative colitis and peptic ulcer. J Saudi Chem Soc. 2013;17(1):101-124. doi:10.1016/j.jscs.2012.03.002

53.   De Jesus NZT. Falcao H de S. Gomes IF. et al. Tannins, peptic ulcers and related mechanisms. Int J Mol Sci. 2012;13(3):3203-3228.

54.   Abdallah IZA. Khattab H. Heeba GH. Gastroprotective Effect of Cordia Myxa L. Fruit Extract against Indomethacin- Induced Gastric Ulceration in Rats. 2011;(May 2015).

55.   Saranya P. Geetha A. Narmadha Selvamathy SMK. A Biochemical Study on the Gastroprotective Effect of Andrographolide in Rats Induced with Gastric Ulcer. www.ijpsonline.com

56.   Pathan IK. Babu KN. Kumar KK. Ishwarya K. Kiran JH. Synthesis and gastroprotective evaluation of new chalcone derivatives. Res J Pharmacol Pharmacodyn. 2013;5(6):325-330.

 

 

Accepted on 05.01.2023           © RJPT All right reserved

Research J. Pharm. and Tech 2023; 16(8):3615-3621.