Toxicity Profiles of Kleeb Bua Daeng Formula, a Traditional Thai Medicine, and Its Protective Effects on Memory Impairment in Animals
Abstract
:1. Introduction
2. Results
2.1. KBD Does Not Induce Cytotoxicity in Human Neuroblastoma Cells (SH-SY5Y)
2.2. KBD Reduced Neuronal Cell Death Induced by Aβ1–42
2.3. KBD Does Not Affect Locomotor Function in Rats
2.4. KBD Protects against Memory Loss in Aβ1–42-Treated Rats
2.4.1. Water Maze Test (MWM)
2.4.2. Object-Recognition Test (ORT)
2.5. KBD Reduces Malondialdehyde (MDA) Levels in Rat Brain
2.6. KBD Enhances Oxidative Enzymes Activity in Rat Brain
2.7. KBD Alters the Level of AChE Activity in Rat Brain
2.8. Acute and Subchronic Toxicological Evaluation
2.8.1. Acute Toxicological Evaluation
2.8.2. Subchronic Toxicological Evaluation
Survival and Clinical Observations
Body Weight and Food Consumption
Hematology Parameters
Serum Biochemical Parameters
The Relative Organ Weight
Histopathological Analysis
3. Discussion
4. Materials and Methods
4.1. Chemicals and Plant Preparation
4.2. The Effects of KBD Formula on Aβ-Induced Cell Damage in Neuroblastoma Cells
4.2.1. Cell Culture
4.2.2. Cytotoxicity Assay
4.2.3. Neuroprotection against Aβ1–42 Toxicity
4.3. The Effects of KBD Formula on Aβ-Induced Memory Deficits in Rats
4.3.1. Animals Preparation
4.3.2. Drug Administration
4.3.3. Neurosurgery and Aβ1–42 Injection
4.3.4. Open-Field Test (OFT)
4.3.5. Object-Recognition (ORT) Test
4.3.6. Morris Water Maze (MWM) Test
4.4. Biochemical Parameter Assay
4.4.1. Determination of Superoxide Dismutase Activity
4.4.2. Determination of Catalase Activity
4.4.3. Determination of Glutathione Peroxidase Activity
4.4.4. Determination of Malondialdehyde Level
4.4.5. AChE Inhibitory Activity Assay
4.5. Acute and Subchronic Toxicological Evaluation
4.5.1. Acute Oral Toxicity Study
4.5.2. Subchronic Oral Toxicity Study in Rats
Pathological Examination
Measurement of Hematological and Biochemical Parameters in Rats
4.6. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameters | Treatment Groups | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Control | 125 mg/kg | 250 mg/kg | 500 mg/kg | Recovery | ||||||
Males | Females | Males | Females | Males | Females | Males | Females | Males | Females | |
RBC, 106/µL | 9.99 ± 0.47 | 9.47 ± 0.28 | 9.88 ± 0.44 | 9.26 ± 0.33 | 9.83 ± 0.32 | 9.39 ± 0.25 | 9.76 ± 0.58 | 9.54 ± 0.42 | 9.68 ± 0.33 | 9.13 ± 0.44 |
HGB, g/dL | 17.38 ± 0.53 | 17.96 ± 0.42 | 17.69 ± 0.71 | 17.50 ± 0.71 | 17.36 ± 0.59 | 17.55 ± 0.50 | 17.30 ± 0.91 | 18.01 ± 0.81 | 17.60 ± 0.39 | 17.04 ± 0.64 |
HCT, % | 59.94 ± 1.78 | 57.46 ± 1.64 | 56.90 ± 2.32 | 56.11 ± 2.42 | 55.06 ± 2.14 | 55.71 ± 1.72 | 55.30 ± 3.19 | 57.56 ± 2.88 | 55.82 ± 1.38 | 53.68 ± 2.19 |
MCV, fl | 55.04 ± 1.58 | 60.67 ± 1.11 | 57.62 ± 1.52 | 60.61 ± 0.77 | 56.01 ± 1.21 | 59.31 ± 1.09 | 56.70 ± 1.19 | 60.33 ± 1.16 | 57.69 ± 1.68 | 58.86 ± 1.46 |
MCH, pg | 17.41 ± 0.47 | 18.97 ± 0.29 | 17.91 ± 0.45 | 18.91 ± 0.29 | 17.65 ± 0.40 | 18.70 ± 0.35 | 17.73 ± 0.41 | 18.88 ± 0.34 | 18.18 ± 0.54 | 18.68 ± 0.35 |
MCHC, g/dL | 31.62 ± 0.30 | 31.26 ± 0.27 | 31.08 ± 0.23 | 31.19 ± 0.36 | 31.53 ± 0.33 | 31.51 ± 0.20 | 31.30 ± 0.35 | 31.28 ± 0.27 | 31.52 ± 0.33 | 31.74 ± 0.28 |
RDW, fl | 32.9 ± 1.10 | 30.54 ± 0.73 | 34.1 ± 1.16 | 30.08 ± 0.68 | 33.19 ± 0.68 | 29.38 ± 0.59 | 33.30 ± 1.31 | 29.59 ± 0.55 | 33.20 ± 0.65 | 29.15 ± 0.48 |
RET, 103/µL | 289.57 ± 19.1 | 323.21 ± 38.98 | 304.65 ± 32.8 | 306.61 ± 45.08 | 297.02 ± 33.1 | 297.93 ± 37.1 | 279.96 ± 21.1 | 324.78 ± 39.57 | 306.92 ± 28.1 | 293.44 ± 50.5 |
PLT, 103/µL | 833.60 ± 81.4 | 757.60 ± 56.51 | 847.70 ± 105 | 770.70 ± 73.14 | 772.80 ± 63.7 | 800.40 ± 57.3 | 838.00 ± 85.3 | 838.90 ± 115.4 | 796.30 ± 62.5 | 842.50 ± 67.4 |
PDW, fl | 8.20 ± 0.35 | 7.97 ± 0.36 | 8.32 ± 0.36 | 8.03 ± 0.22 | 8.00 ± 0.39 | 8.15 ± 0.31 | 8.69 ± 0.52 | 8.37 ± 0.35 | 8.91 ± 0.33 | 8.15 ± 0.30 |
MPV, fl | 6.94 ± 0.24 | 7.01 ± 0.24 | 7.13 ± 0.19 | 7.02 ± 0.14 | 6.83 ± 0.26 | 6.99 ± 0.20 | 7.29 ± 0.30 | 7.16 ± 0.13 | 7.54 ± 0.18 | 7.05 ± 0.20 |
WBC, 103/µL | 7.94 ± 0.97 | 6.92 ± 1.42 | 9.78 ± 1.33 | 6.21 ± 0.89 | 7.58 ± 1.29 | 5.63 ± 1.32 | 7.23 ± 2.53 | 7.14 ± 1.21 | 8.78 ± 1.30 | 6.65 ± 1.08 |
NEU, 103/µL | 0.87 ± 0.15 | 0.47 ± 0.18 | 0.90 ± 0.42 | 0.26 ± 0.16 | 0.73 ± 0.42 | 0.46 ± 0.25 | 0.55 ± 0.36 | 0.42 ± 0.16 | 1.01 ± 0.15 | 0.48 ± 0.08 |
LYMPH,103/µL | 6.58 ± 0.83 | 6.04 ± 1.20 | 8.35 ± 1.44 | 5.65 ± 0.82 | 6.27 ± 1.33 | 4.83 ± 1.07 | 6.22 ± 2.46 | 6.32 ± 1.07 | 7.17 ± 1.14 | 5.81 ± 1.00 |
MONO,103/µL | 0.41 ± 0.18 | 0.36 ± 0.12 | 0.45 ± 0.12 | 0.27 ± 0.05 | 0.46 ± 0.12 | 0.30 ± 0.09 | 0..38 ± 0.16 | 0.35 ± 0.07 | 0.48 ± 0.11 | 0.31 ± 0.06 |
EO, 103/µL | 0.07 ± 0.03 | 0.05 ± 0.03 | 0.07 ± 0.03 | 0.03 ± 0.01 | 0.10 ± 0.03 | 0.04 ± 0.02 | 0.07 ± 0.02 | 0.04 ± 0.01 | 0.10 ± 0.02 | 0.04 ± 0.02 |
BASO, 103/µL | 0.01 ± 0.01 | 0.01 ± 0.01 | 0.02 ± 0.02 | 0.01 ± 0.01 | 0.02 ± 0.01 | 0.01 ± 0.01 | 0.01 ± 0.01 | 0.01 ± 0.01 | 0.01 ± 0.01 | 0.01 ± 0.01 |
Parameters | Treatment Groups | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Control | 125 mg/kg | 250 mg/kg | 500 mg/kg | Recovery | ||||||
Males | Females | Males | Females | Males | Females | Males | Females | Males | Females | |
GLU | 299.7 ± 72.3 | 148.8 ± 73.7 | 350.5 ± 43.1 | 172.7 ± 97.5 | 318.5 ± 57.5 | 150.4 ± 45.6 | 324.2 ± 66.2 | 186.9 ± 69.8 | 396.1 ± 57.8 | 148.3 ± 60.7 |
BUN | 21.1 ± 1.7 | 21.0 ± 2.7 | 21.2 ± 1.3 | 21.1 ± 1.8 | 21.7 ± 2.5 | 22.4 ± 2.7 | 23.0 ± 2.0 | 23.0 ± 2.8 | 24.4 ± 2.9 | 23.2 ± 4.3 |
CREA | 0.4 ± 0.0 | 0.5 ± 0.1 | 0.4 ± 0.0 | 0.5 ± 0.0 | 0.4 ± 0.0 | 0.5 ± 0.0 | 0.4 ± 0.0 | 0.4 ± 0.0 | 0.5 ± 0.0 | 0.5 ± 0.1 |
UA | 6.9 ± 1.4 | 4.1 ± 0.8 | 7.6 ± 0.8 | 4.3 ± 0.9 | 7.6 ± 1.3 | 3.9 ± 0.3 | 6.7 ± 1.3 | 4.5 ± 1.1 | 8.7 ± 1.0 | 4.5 ± 0.4 |
CHOL | 87.9 ± 17.8 | 99.6 ± 15.9 | 87.7 ± 7.6 | 104.7 ± 15.4 | 89.0 ± 11.3 | 107.2 ± 12.6 | 93.6 ± 11.4 | 117.9 ± 14.1 | 94.6 ± 22.0 | 106.6 ± 20.2 |
TG | 110.2 ± 21.7 | 68.8 ± 15.2 | 111.9 ± 28.3 | 78.5 ± 16.8 | 128.7 ± 34.4 | 78.8 ± 20.1 | 128.5 ± 29.8 | 103.0 ± 32.0 | 143.5 ± 29.8 | 76.1 ± 19.2 |
AST | 99.7 ± 16.2 | 99.3 ± 17.1 | 100.1 ± 23.4 | 90.5 ± 9.7 | 110.6 ± 28.2 | 96.7 ± 9.8 | 94.8 ± 16.4 | 96.3 ± 11.0 | 157.6 ± 39.5 | 102.4 ± 10.0 |
ALT | 54.6 ± 14.2 | 38.9 ± 4.4 | 61.9 ± 21.5 | 38.3 ± 4.3 | 70.9 ± 25.0 | 44.9 ± 8.0 | 57.3 ± 22.7 | 40.5 ± 4.5 | 101.4 ± 30.4 | 48.7 ± 3.6 |
ALP | 66.6 ± 5.3 | 32.8 ± 3.3 | 69.3 ± 10.8 | 33.0 ± 3.2 | 69.9 ± 11.7 | 35.2 ± 0.2 | 68.0 ± 8.0 | 33.0 ± 4.0 | 73.8 ± 8.9 | 32.1 ± 6.5 |
TP | 6.9 ± 0.2 | 7.3 ± 0.2 | 7.3 ± 0.2 | 7.3 ± 0.3 | 7.2 ± 0.3 | 7.2 ± 0.2 | 7.4 ± 0.7 | 7.5 ± 0.3 | 8.3 ± 0.5 | 8.0 ± 0.5 |
ALB | 5.3 ± 0.2 | 5.9 ± 0.1 | 5.6 ± 0.2 | 5.7 ± 0.1 | 5.4 ± 0.2 | 5.6 ± 0.2 | 5.4 ± 0.2 | 5.5 ± 0.3 | 5.7 ± 0.2 | 5.8 ± 0.2 |
GLO | 1.7 ± 0.1 | 1.4 ± 0.1 | 1.7 ± 0.3 | 1.4 ± 0.2 | 1.8 ± 0.2 | 1.6 ± 0.3 | 1.8 ± 0.3 | 1.8 ± 0.2 | 2.5 ± 0.4 | 2.1 ± 0.3 |
Parameters | Treatment Groups | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Control | 125 mg/kg | 250 mg/kg | 500 mg/kg | Recovery | ||||||
Males | Females | Males | Females | Males | Females | Males | Females | Males | Females | |
Adrenal GI (L) | 0.0448 ± 0.0024 | 0.0476 ± 0.0057 | 0.0475 ± 0.0062 | 0.0492 ± 0.0039 | 0.044 ± 0.0035 | 0.0488 ± 0.0033 | 0.0431 ± 0.0044 | 0.047 ± 0.0037 | 0.0413 ± 0.0033 | 0.0451 ± 0.0041 |
Adrenal GI (R) | 0.0394 ± 0.0031 | 0.0431 ± 0.0030 | 0.0414 ± 0.0050 | 0.044 ± 0.0051 | 0.0377 ± 0.0029 | 0.0441 ± 0.0068 | 0.0356 ± 0.0031 | 0.0432 ± 0.0055 | 0.0372 ± 0.0043 | 0.0404 ± 0.0036 |
Epididymis/ Ovary (L) | 0.6055 ± 0.0853 | 0.0498 ± 0.0059 | 0.6107 ± 0.0589 | 0.0483 ± 0.0082 | 0.5919 ± 0.0691 | 0.0507 ± 0.0079 | 0.5995 ± 0.0216 | 0.0539 ± 0.0106 | 0.5239 ± 0.0582 | 0.0478 ± 0.0042 |
Epididymis/ Ovary(R) | 0.6041 ± 0.0421 | 0.0508 ± 0.0051 | 0.5953 ± 0.0935 | 0.0483 ± 0.0059 | 0.5788 ± 0.0405 | 0.0526 ± 0.0090 | 0.5977 ± 0.0272 | 0.0556 ± 0.0120 | 0.5197 ± 0.0309 | 0.0461 ± 0.0083 |
Thymus | 0.3293 ± 0.0415 | 0.2449 ± 0.0523 | 0.3189 ± 0.0605 | 0.265 ± 0.0460 | 0.3198 ± 0.0511 | 0.2689 ± 0.0679 | 0.3139 ± 0.0388 | 0.2553 ± 0.0596 | 0.3113 ± 0.0424 | 0.2441 ± 0.0374 |
Spleen | 0.9386 ± 0.1238 | 0.6466 ± 0.0479 | 0.9613 ± 0.0877 | 0.6531 ± 0.0456 | 0.9154 ± 0.0966 | 0.6713 ± 0.0617 | 0.9475 ± 0.0787 | 0.6787 ± 0.0659 | 0.9126 ± 0.0546 | 0.5612 ± 0.1796 |
Uterus | - | 0.596 ± 0.1914 | - | 0.5619 ± 0.2389 | - | 0.6254 ± 0.2990 | - | 0.7185 ± 0.2096 | - | 0.4648 ± 0.1352 |
Heart | 1.4229 ± 0.0938 | 0.9203 ± 0.0617 | 1.4563 ± 0.1552 | 0.935 ± 0.0590 | 1.3984 ± 0.0730 | 0.9209 ± 0.0554 | 1.3681 ± 0.0731 | 0.9121 ± 0.0591 | 1.5039 ± 0.0481 | 0.9422 ± 0.0445 |
Kidney (L) | 1.2634 ± 0.0697 | 0.7417 ± 0.0377 | 1.2676 ± 0.1247 | 0.7477 ± 0.0309 | 1.1942 ± 0.0917 | 0.7392 ± 0.0307 | 1.2238 ± 0.0941 | 0.7161 ± 0.1934 | 1.2276 ± 0.0823 | 0.7489 ± 0.0447 |
Kidney (R) | 1.2944 ± 0.0842 | 0.7816 ± 0.0465 | 1.2705 ± 0.1355 | 0.778 ± 0.0545 | 1.2197 ± 0.0874 | 0.7655 ± 0.0328 | 1.2338 ± 0.1104 | 0.8047 ± 0.0681 | 1.2604 ± 0.0750 | 0.781 ± 0.0427 |
Testis (L) | 1.8789 ± 0.1077 | - | 1.9031 ± 0.1869 | - | 1.8457 ± 0.1417 | - | 1.8802 ± 0.1077 | - | 1.8824 ± 0.0711 | - |
Testis (R) | 1.8803 ± 0.0737 | - | 1.874 ± 0.1740 | - | 1.7906 ± 0.1309 | - | 1.8368 ± 0.1234 | - | 1.8592 ± 0.0967 | - |
Brain | 2.2057 ± 0.0527 | 1.9893 ± 0.1008 | 2.1515 ± 0.0603 | 2.0147 ± 0.0483 | 2.1639 ± 0.0836 | 1.9874 ± 0.0633 | 2.19 ± 0.0792 | 2.0344 ± 0.0578 | 2.2028 ± 0.0779 | 2.0501 ± 0.0385 |
Liver | 13.2839 ± 0.9141 | 7.1394 ± 0.5813 | 13.7123 ± 1.6271 | 6.7335 ± 1.8537 | 13.0735 ± 0.6401 | 7.113 ± 0.6302 | 13.698 ± 0.9184 | 7.6398 ± 0.9619 | 13.3958 ± 0.8096 | 7.0372 ± 0.7335 |
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Waiwut, P.; Kengkoom, K.; Pannangrong, W.; Musigavong, N.; Chheng, C.; Plekratoke, K.; Taklomthong, P.; Nillert, N.; Pitiporn, S.; Kwankhao, P.; et al. Toxicity Profiles of Kleeb Bua Daeng Formula, a Traditional Thai Medicine, and Its Protective Effects on Memory Impairment in Animals. Pharmaceuticals 2022, 15, 988. https://doi.org/10.3390/ph15080988
Waiwut P, Kengkoom K, Pannangrong W, Musigavong N, Chheng C, Plekratoke K, Taklomthong P, Nillert N, Pitiporn S, Kwankhao P, et al. Toxicity Profiles of Kleeb Bua Daeng Formula, a Traditional Thai Medicine, and Its Protective Effects on Memory Impairment in Animals. Pharmaceuticals. 2022; 15(8):988. https://doi.org/10.3390/ph15080988
Chicago/Turabian StyleWaiwut, Pornthip, Kanchana Kengkoom, Wanassanun Pannangrong, Natdanai Musigavong, Chantha Chheng, Kusawadee Plekratoke, Pitchayakarn Taklomthong, Nutchareeporn Nillert, Supaporn Pitiporn, Pakakrong Kwankhao, and et al. 2022. "Toxicity Profiles of Kleeb Bua Daeng Formula, a Traditional Thai Medicine, and Its Protective Effects on Memory Impairment in Animals" Pharmaceuticals 15, no. 8: 988. https://doi.org/10.3390/ph15080988
APA StyleWaiwut, P., Kengkoom, K., Pannangrong, W., Musigavong, N., Chheng, C., Plekratoke, K., Taklomthong, P., Nillert, N., Pitiporn, S., Kwankhao, P., Daodee, S., Chulikhit, Y., Montakantirat, O., & Boonyarat, C. (2022). Toxicity Profiles of Kleeb Bua Daeng Formula, a Traditional Thai Medicine, and Its Protective Effects on Memory Impairment in Animals. Pharmaceuticals, 15(8), 988. https://doi.org/10.3390/ph15080988