Study on chemical composition, toxicity and some biological effects supporting the treatment of gastric and duodenal ulcers of Sanchezia nobilis Hook.F. leaves

LIST OF TABLES

Table 1.1. Species composition and distribution of genus Sanchezia 4

Table 1. 2. Published chemical compositions of Sanchezia genus in the world and Vietnam...16 Table 2. 1. Dose levels for testing biological effects of total extract and fractions

40 Benzene leaves

Table 3.1. 1H and 13C NMR spectral data of compound SXH1 and reference substance 56

Table 3.2. 1H and 13C NMR spectral data of compound SXH2 and reference substance 58

Table 3.3. 1H and 13C NMR spectral data of compound SXH3 and reference substance 60

Table 3.4. 1H and 13C NMR spectral data of compound SXH4 61

Table 3.5. 1H and 13C-NMR spectral data of compound SXH6 and reference substance 63

Table 3.6. 1H and 13C-NMR spectral data of compound SXH7 and reference substance 65

Table 3.7. 1H and 13C-NMR spectral data of compound SXE8 and reference substance 67

Table 3.8. 1H and 13C-NMR spectral data of compound SXE9 69

Table 3.9. 1H and 13C-NMR spectral data of compound SXE10 and reference ...71 Table 3.10. 1H and 13C-NMR spectral data of compound SXE11 and reference ...72 Table 3.11. 1H and 13C-NMR spectral data of compound SXE12 and reference ...73 Table 3.12. 1H and 13C-NMR spectral data of compound SXE13 and reference ...74 Table 3.13. 1H and 13C-NMR spectral data of compound SXE14 and reference ...76 Table 3.14. 1H and 13C-NMR spectral data of compound SXE15 and reference ...77 Table 3.15. 1H and 13C-NMR spectral data of compound SXE16 and reference substance .79 Table 3.16. 1H and 13C-NMR spectral data of compound SXE17 and reference substance ...80 Table 3.17. 1H and 13C-NMR spectral data of compound SXE18 and reference substance ...82 Table 3.18. 1H and 13C-NMR spectral data of compound SXE19 and reference substance .84 Table 3.19. 1H and 13C-NMR spectral data of compound SXE20 and reference substance .85 Table 3.20. 1H and 13C-NMR spectral data of compound SXE22 and reference substance .87 Table 3.21. Acute toxicity test results of the extract fractions from Xăng xê leaves ...88 Table 3.22. Effect of ethyl acetate extract on body weight of mice 90

Table 3.23. Effect of ethyl acetate extract on hematopoietic ability 91

Table 3.24. Effect of ethyl acetate extract on white blood cell count and white blood cell formula 92

Table 3.25. Effect of ethyl acetate extract on platelet count in mouse blood 93

Table 3.26. Effects of ethyl acetate extract on the level of liver cell damage (AST/ALT)...93 Table 3.27. Effects of ethyl acetate extract on liver function (bilirubin, albumin, total cholesterol in mouse blood) 94

Table 3.28. Effects of ethyl acetate extract on kidney function 95

Table 3.29. Microscopic image of mouse liver 95

Table 3.30. Microscopic image of mouse kidney 96

Table 3.31. Percentage of rats with ulcers after pyloric ligation 97

Table 3.32. Effect of total extract on severity of ulcer lesions 97

Table 3.33. Effect of total extract on average ulcer score, ulcer index 98

Table 3.34. Effect of total extract sample on gastric juice volume, 99

Table 3.35. Gross and microscopic images of mouse stomachs in each batch of 100

Table 3.36. Percentage of rats with ulcers after pyloric ligation 102

Table 3.37. Effect of fractionated samples on the severity of ulcer lesions 102

Table 3.38. Effect of high fraction samples on ulcer score 103

Table 3.39. Effects of fractionated samples on gastric juice volume, free acidity, total acidity and gastric juice pH 104

Table 3.40. Gross and microscopic images of mouse stomachs in each batch of 105

Table 3.41. Effects of 4 total extract samples and fractions on the temperature response time of white mice 107

Table 3.42. Effects of 4 total and fractional samples on pain force on 108 pain threshold meter

Table 3.43. Effects of 4 total extract samples and fractions on 109

LIST OF IMAGES

Figure 1.1. Image of Sanchezia noilis Hook.f 6

Figure 1.2. Drawing depicting the microanatomy of leaf 8

Figure 1.3. Drawing depicting the microanatomy of the 8th stem.

Figure 1.4. Drawing depicting the microscopic anatomy of flower 9

Figure 1.5. Flavonoid compounds isolated from the genus Sanchezia 11

Figure 1.6. Phenolic compounds isolated from the genus Sanchezia 13

Figure 1.7. Organic acid and glycoside compounds isolated from Sanchezia genus 15

Figure 1.8. Terpene compounds isolated from the genus Sanchezia 15

Figure 1.9. Other compounds isolated from the genus Sanchezia 16

Figure 2.1. Study design diagram 38

Figure 3.1. Image of the Xang Xe tree in Nam Dinh 47

Figure 3.2. Characteristics of vegetative organs of the Xang xe 48 plant

Figure 3.3. Characteristics of reproductive organs of the Xang xe 48 plant

Figure 3.4. Schematic diagram of fractional extraction of leaves of Xang xe 52

Figure 3.5. Isolation diagram of n- hexane 53 high fraction compounds

Figure 3.6. Diagram of isolation of alkaloid-rich extracts of ethyl acetate extract 54

Figure 3.7. Diagram of isolation of compounds of ethyl acetate extract (E2) after removing the alkaloid part (E1) 55

Figure 3.8. Chemical structure of compound SXH1 57

Figure 3.9. Chemical structure of compound SXH2 59

Figure 3.10. Chemical structure of compound SXH3 60

Figure 3.11. Chemical structure of compound SXH4 62

Figure 3.12. Chemical structure of compound SXH6 64

Figure 3.13. Chemical structure of compound SXH7 66

Figure 3.14. Chemical structure of compound SXE8 67

Figure 3.15. Preliminary structure prediction of compound SXE9 68

Figure 3.16. Chemical structure, HMBC, COSY and NOESY interactions of SXE9 70

Figure 3.17. Chemical structure of compound SXE10 71

Figure 3.18. Chemical structure of compound SXE11 72

Figure 3.19. Chemical structure of compound SXE12 74

Figure 3.20. Chemical structure of compound SXE13 75

Figure 3.21. Chemical structure of compound SXE14 76

Figure 3.22. Chemical structure of compound SXE15 78

Figure 3.23. Chemical structure of compound SXE16 79

Figure 3.24. Chemical structure of compound SXE17 81

Figure 3.25. Chemical structure of compound SXE18 83

Figure 3.26. Chemical structure of compound SXE19 84

Figure 3.27. Chemical structure of compound SXE20 86

Figure 3.28. Chemical structure of compound SXE22 88

Figure 4.1. Chemical structures of 20 compounds isolated from the leaves of the plant Xang xe 113

Figure 4.2. Anti-inflammatory activities of quercetin in experimental models 123

PROBLEM STATEMENT

Currently, scientists around the world have recorded the presence of more than

390,000 plant species, of which at least 30,000 species are believed to have effects and about 17,810 species have medicinal uses [178]. Plant species contain about 5 million chemical compounds. In Vietnam, there are about 5,100 plant species used as medicine [7]. East Asia, China, Japan and India are the countries with the most experience in using and consuming oriental medicine. Vietnam has a long tradition of using oriental medicine and the demand for oriental medicine is still very large. Since the first chemical drugs appeared, several thousand active ingredients have been used as drugs. This development has brought about many great effects in treatment, but it has also gradually eroded the experience of using medicinal plants. The use of chemical drugs always has many potential unwanted effects, especially in cases of simultaneous illness. Therefore, nowadays, the research and use of drugs derived from medicinal herbs are developing strongly. The combination of scientific and technical advances with the experience of using medicinal plants among the people will create new drugs that are safer and more effective, as well as help people understand more about nature. Therefore, many species of plants, animals and minerals have been studied, but this number accounts for a very small proportion, and there are also plant species that have been studied a lot, but when studied more deeply, they still give new information.

interesting discovery that needs further exploration.

The scientific name of the Sanchezia nobilis Hook.f. plant (family Acanthaceae) [3]. There have not been many studies on the chemical composition and biological effects of the plant. Some species of the Sanchezia genus are used in folk medicine in many countries to treat convulsions, sedation, cough with phlegm, anti-tuberculosis and anti-cancer [22]. This plant is widely used in India and Bangladesh for snake bites, malaria, dysentery, diarrhea, liver dysfunction [146]. In addition, in Thailand, the Sanchezia plant is used as a food with the effect of stabilizing pregnancy, enriching blood, treating menstrual cramps [123]... In Vietnam, people use the Sanchezia plant as a medicine to treat stomach ulcers, duodenal ulcers, taking a few fresh leaves, washing them and eating them with salt will reduce the pain.

pain, use for a while to have effect, or can boil dry leaves to drink daily instead of water. However, up to now, there has been no systematic research on the effect on gastric and duodenal ulcers of Xăng xê leaves in the world as well as in Vietnam. From the above reality to provide more scientific evidence for people's use, the thesis conducts the topic: " Research on chemical composition, toxicity and some biological effects supporting the treatment of gastric and duodenal ulcers of Xăng xê leaves ( Sanchezia nobilis Hook.f.) '' with the following objectives:

Objective 1 : Isolate and determine the chemical structure of some compounds from the leaves of the Xang xe tree.

Objective 2 : Evaluate the toxicity, anti-ulcer and central analgesic effects of the total extract and leaf fractions of Xang xe.

To achieve the above objectives, the thesis carries out the following 3 contents:

1. About botany

- Describe morphological characteristics and identify scientific names of research samples.

2. About chemical composition

- Extraction, isolation and structural determination of biologically active compounds of Xang xe leaves.

3. On toxicity and biological effects

- Determine the acute toxicity of the total extract and leaf fractions of Xang xe.

- Determine the subchronic toxicity of the most effective and potentially toxic fraction of the leaves of Xăng xê.

- Evaluate the anti-gastroduodenal ulcer effect of the whole extract and leaf fractions of Xang xe.

- Evaluation of the central analgesic effect of the whole extract and leaf fractions of Cynomorium barbata.

CHAPTER 1. OVERVIEW

1.1. Classification position, botanical characteristics and distribution of the genus Sanchezia

1.1.1.Classification position of genus Sanchezia

According to the "Classification system of the Magnoliophyta " by author A.Takhtajan, Sanchezia nobilis Hook.f. has the following classification position [68]: Kingdom Plantae, Division Magnolipphyta, Subclass Magnoliidae Novák ex Takht, Order Lamiales, Family Acanthaceae, Genus Sanchezia, Species Sanchezia nobilis Hook.f.

1.1.2. Species composition and distribution of the genus Sanchezia

The genus Sanchezia is mainly distributed in the western part of South America. The center of species diversity of the genus is located in Peru and Ecuador. A few species are distributed in the north and east of North America, Central America and the Caribbean. But today the genus is cultivated in many places and is considered native in some places such as Vietnam, Cuba, Bangladesh...[220]. The genus Sanchezia was first described by Ruiz and Pavón in 1794 with two species. In 1964, this genus was revised by Emery C. Leonard and Lyman B. Smith, with 59 species, of which 26 were described for the first time, and at the same time published the taxonomic keys for these 59 species [215]. In 2015, EA Tripp and DM Koenemann re-analyzed the development history of the genus Sanchezia and listed 55 species [91]. On the “Plants of the world online” page [220] as of October 15, 2022, the genus Sanchezia is listed with 70 results including 1 genus name and 69 species names, of which 44 species are accepted. In a recent publication by Igor and Pedro [103], 11 more synonyms were identified, suggesting that the genus Sanchezia has 44 species. The taxonomic key results according to Igor and Pedro and the “Plants of the world online” page are completely identical. On the “Plants of the world online” page, Sanchezia oblonga has 11 synonyms: S. hirsuta Pers, Ancylogyne peruviana Nees, S. bicolor Leonard & LBSm, S. flava Leonard, S. helophila Leonard & LBSm, S. macbridei Leonard, S. megalia Leonard & LBSm., S. nobilis Hook.f., S. nobilis var. glaucophylla Lem, S. peruviana (Nees) Rusby, S. speciosa Leonard. Thus, the three species names studied and published in the genus S. nobilis , S. speciosa and S. oblonga are determined to be synonyms.

Table 1.1. Species composition and distribution of the genus Sanchezia

STT

Species name	Distribution	TLTK
1	Sanchezia arborea Leonard & LB Sm.	Peru	b
2	Sanchezia aurantiaca Leonard & LB Sm.	Peru	a, b, c
3	Sanchezia aurea Leonard & LB Sm.	Peru	a, b, c
4	Sanchezia bicolor Leonard & LB Sm.	Peru	b
5	Sanchezia capitata (Nees) Lindau	Peru	b
6	Sanchezia coccinea Leonard & LB Sm.	Peru	a, b, c
7	Sanchezia coleifolia Leonard & LB Sm.	Ecuador	a, b, c
8	Sanchezia conferta Leonard, J. Wash	Peru	a, b, c
9	Sanchezia cyathibractea Mildbr.	Peru	b
10	Sanchezia dasia Leonard & LB Sm.	Peru	a, b, c
11	Sanchezia decora Leonard & LB Sm.	Peru	b
12	Sanchezia ecuadorensis Leonard, J.Wash	Ecuador	a, b, c
13	Sanchezia ferreyrae Leonard & LB Sm.	Peru	a, b, c
14	Sanchezia filamentosa Lindau	Peru	a, b, c
15	Sanchezia flava Leonard, J. Wash	Peru	b
16	Sanchez Foster Wash	Peru	a, b, c
17	Sanchezia killipii Leonard, J.Wash	Peru	a, b, c
18	Sanchezia klugii Leonard & LB Sm.	Peru	a, b, c
19	Sanchezia lampra Leonard & LB Sm.	Ecuador	a, b, c
20	Sanchezia lasia Leonard & LB Sm.	Peru	a, b, c
21	Sanchezia lispa Leonard & LB Sm.	Peru	a, b, c
22	Sanchezia longiflora Hook. f., Planch.	Ecuador, Peru	a, b, c
23	Sanchezia loranthifolia Lindau	Peru, Brazil	a, b, c
24	Sanchezia macrocnemis Nees Wassh	Peru, Ecuador, Brazil…	a, c
25	Sanchezia lutea Leonard	Colombia	b
26	Sanchezia megalia Leonard & LB Sm.	Peru	b
27	Sanchezia munita Nees, Planch.	Brazil	a, b, c
28	Sanchezia oblonga Ruiz & Pav. Sanchezia nobilis Hook.f	Ecuador, Vietnam, Bangladesh Brazil,…	a, b, c
29	Sanchezia ovata Ruiz & Pav.	Peru, Bolivia, Brazil	a, b, c
30	Sanchezia parvibracteata Sprague & Hutch	Sri Lanka, Belize, Bolivia…	a, b, c

Maybe you are interested!

Sanchezia parviflora Leonard, J.Wash	Ecuador, Colombia	a, b, c
32	Sanchezia pedicellata Leonard & LB Sm.	Peru	a, b, c
33	Sanchezia pennellii Leonard, J.Wash	Colombia	b
34	Sanchezia pulchra Leonard, J. Wash	Peru	a, b, c
35	Sanchezia punicea Leonard & LB Sm.	Peru	a, b, c
36	Sanchezia putumayensis Leonard	Colombia, Bolivia, Ecuador, Peru	a, b, c
37	Sanchezia rhodochroa Leonard & LB Sm.	Peru	a, b, c
38	Sanchezia rosea Leonard, J. Wash	Peru	a, b, c
39	Sanchezia rubriflora Leonard	Peru	a, c
40	Sanchezia sanmartinensis Leonard & LB Sm.	Peru	a, b, c
41	Sanchezia scandens Leonard & LB Sm.	Peru, Brazil , Colombia, Ecuador	a, b, c
42	Sanchezia sericea Leonard, J.Wash	Ecuador	a, b, c
43	Sanchezia siraensis Leonard, J.Wash	Peru	a, b, c
44	Sanchezia skutchii Leonard & LB Sm.	Ecuador	b
45	Sanchezia speciosa Leonard, J.Wash	Cuba	b
46	Sanchezia sprucei Lindau	Peru	a, b, c
47	Sanchezia stenantha Leonard, J. Wash	Peru	b
48	Sanchezia stenomacra Leonard & LB Sm.	Peru	b
49	Sanchezia sylvestris Leonard, J. Wash	Peru	a, b, c
50	Sanchezia tarapotensis Leonard & LBSm.	Peru	a, b, c
51	Sanchezia thinophila Leonard	Columbia	a, b, c
52	Sanchezia tigrina Leonard, J. Wash	Peru	a, b, c
53	Sanchezia villosa Leonard & LB Sm.	Peru	a, b, c
54	Sanchezia williamsii Leonard, J. Wash	Peru	a, b, c
55	Sanchezia woytkowskii Leonard & LB Sm.	Peru	a, b, c
56	Sanchezia wurdackii Wassh	Peru	a, b, c
57	Sanchezia xantha Leonard & LB Sm.	Peru	a, b, c

Study on chemical composition, toxicity and some biological effects supporting the treatment of gastric and duodenal ulcers of Sanchezia nobilis Hook.F. leaves - 2

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